Novel mutations in the BRCA1 and BRCA2 genes in Iranian women with early-onset breast cancer

BACKGROUND: Breast cancer is the most common female malignancy and a major cause of death in middle-aged women. So far, germline mutations in the BRCA1 and BRCA2 genes in patients with early-onset breast and/or ovarian cancer have not been identified within the Iranian population. METHODS: With the collaboration of two main centres for cancer in Iran, we obtained clinical information, family history and peripheral blood from 83 women under the age of 45 with early-onset breast cancer for scanning of germline mutations in the BRCA1 and BRCA2 genes. We analysed BRCA1 exons 11 and BRCA2 exons 10 and 11 by the protein truncation test, and BRCA1 exons 2, 3, 5, 13 and 20 and BRCA2 exons 9, 17, 18 and 23 with the single-strand conformation polymorphism assay on genomic DNA amplified by polymerase chain reaction. RESULTS: Ten sequence variants were identified: five frameshifts (putative mutations – four novel); three missense changes of unknown significance and two polymorphisms, one seen commonly in both Iranian and British populations. CONCLUSIONS Identification of these novel mutations suggests that any given population should develop a mutation database for its programme of breast cancer screening. The pattern of mutations seen in the BRCA genes seems not to differ from other populations studied. Early-onset breast cancer (less than 45 years) and a limited family history is sufficient to justify mutation screening with a detection rate of over 25% in this group, whereas sporadic early-onset breast cancer (detection rate less than 5%) is unlikely to be cost-effective

Matrix augmentation as an efficient method for resolving interaction of bromocriptine with human serum albumin: trouble shooting and simultaneous resolution

This work reports the results of an interesting study related to the investigation of interactions of bromocriptine (BCP) with human serum albumin (HSA) by mathematicall modelling of voltammetric and spectroscopic data into an augmented data matrix and its resolution by multivariate curve resolution-alternating least squares (MCR-ALS). The quality of the results obtained by MCR-ALS was examined by MCR-BANDS and its outputs confirmed the absence of rotational ambiguities in the MCR-ALS results. BCP-HSA interactions were also modeled by molecular docking methods to verify the results obtained from experimental sections and fortunately, they were compatible. Hard modeling of the experimental data by EQUISPEC helped us to calculate the binding constant of the complex formed from BCP-HSA interactions which was in a good agreement with that of calculated from direct analysis of the experimental data. Finally, with the help of two different amperometric measurements based on BCP-HSA interactions a novel electroanalytical method was developed for biosensing of HSA in serum samples.Fil: Jalalvand, Ali R.. Kermanshah University of Medical Sciences; IránFil: Ghobadi, Sirous. Kermanshah University of Medical Sciences; IránFil: Goicoechea, Hector Casimiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Desarrollo Analítico y Quimiometría; ArgentinaFil: Faramarzi, Elahe. Kermanshah University of Medical Sciences; IránFil: Mahmoudi, Majid. Kermanshah University of Medical Sciences; Irá

Mathematical modeling of interactions of cabergoline with human serum albumin for biosensing of human serum albumin

In this work, we are going to study the interactions of cabergoline (CBG) with human serum albumin (HSA) by mathematical modeling of voltammetric and spectroscopic data. To achieve this goal, voltammetric and spectroscopic data will be augmented into a data matrix which will be resolved by multivariate curve resolution-alternating least squares (MCR-ALS) as a powerful chemometric tool. Then, the quality of the data fitting by MCR-ALS will be examined by MCR-BANDS to ensure about the absence of the rotational ambiguities in the results. Molecular docking will also be used to model the interactions of CBG with HSA for verifying the results obtained from experimental methods. Hard-modeling of the experimental data will be performed by EQUISPEC to compute the binding constant of the complex formed from the interactions of CBG with HSA for verifying the binding constant obtained by direct analysis of the experimental data. Finally, two chrono-amperometric measurements based on CBG-HSA interactions will be performed to develop a novel electroanalytical method for determination of electro-inactive HSA.Fil: Jalalvand, Ali R.. Kermanshah University of Medical Sciences; IránFil: Ghobadi, Sirous. Razi University; IránFil: Akbari, Vali. Razi University; Irán. Kermanshah University of Medical Sciences; IránFil: Goicoechea, Hector Casimiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Desarrollo Analítico y Quimiometría; ArgentinaFil: Faramarzi, Elahe. Kermanshah University of Medical Sciences; IránFil: Mahmoudi, Majid. Kermanshah University of Medical Sciences; Irá

Effects of hunger state on flavour pleasantness conditioning at home: flavour-nutrient learning vs. flavour-flavour learning

This study examined acquired liking of flavour preferences through flavour-flavour and flavour-nutrient learning under hungry or sated conditions in a naturalistic setting. Each participant consumed one of three versions of a test drink at home either before lunch or after lunch: minimally sweetened (CONTROL: 3% sucrose, 40kcal), artificially sweetened (3% sucrose 40kcal plus artificial sweeteners ASPARTAME) and sucrose-sweetened (SUCROSE: 9.9% sugar, 132kcal). The test drink was an uncarbonated peach-flavoured iced tea served in visually identical drink cans (330ml). Participants preselected as "sweet likers" evaluated the minimally sweetened flavoured drink (conditioned stimulus, CS) in the same state (hungry or sated) in which they consumed the test drink at home. Overall, liking for the CS flavour increased in participants who consumed the SUCROSE drink, however, this increase in liking was significantly larger when tested and trained hungry than sated, consistent with a flavour-nutrient model. Overall increases in pleasantness for the CS flavour in participants who consumed the SUCROSE drink when sated or the ASPARTAME drink independent of hunger state, suggest that flavour-flavour learning also occurred. These results are discussed in light of current learning models of flavour preference

Chemosensory Event-Related Potentials in Response to Nasal Propylene Glycol Stimulation

Propylene glycol, also denoted as 1.2 propanediol (C3H8O2), often serves as a solvent for dilution of olfactory stimuli. It is supposed to serve as a neutral substance and has been used in many behavioral and electrophysiological studies to dilute pure olfactory stimuli. However, the effect of propylene glycol on perception and on neuronal responses has hitherto never been studied. In this study we tested by means of a threshold test, whether a nasal propylene glycol stimulation is recognizable by humans. Participants were able to recognize propylene glycol at a threshold of 42% concentration and reported a slight cooling effect. In addition to the threshold test, we recorded electroencephalography (EEG) during nasal propylene glycol stimulation to study the neuronal processing of the stimulus. We used a flow olfactometer and stimulated 15 volunteers with three different concentrations of propylene glycol (40 trials each) and water as a control condition (40 trials). To evaluate the neuronal response, we analyzed the event-related potentials (ERPs) and power modulations. The task of the volunteers was to identify a change (olfactory, thermal, or tactile) in the continuous air flow generated by the flow olfactometer. The analysis of the ERPs showed that propylene glycol generates a clear P2 component, which was also visible in the frequency domain as an evoked power response in the theta-band. The source analysis of the P2 revealed a widespread involvement of brain regions, including the postcentral gyrus, the insula and adjacent operculum, the thalamus, and the cerebellum. Thus, it is possible that trigeminal stimulation can at least partly account for sensations and brain responses elicited by propylene glycol. Based on these results, we conclude that the use of high propylene glycol concentrations to dilute fragrances complicates the interpretation of presumed purely olfactory effects

Acquired flavor acceptance and intake facilitated by monosodium glutamate in humans

Monosodium glutamate (MSG) is known to enhance liking for the flavor of savory foods, but whether associations between flavors and effects of MSG lead to changes in subsequent liking and intake for the flavor alone is unclear. To test this, 32 volunteers evaluated and consumed a novel savory soup with no added MSG before and after four training sessions where the same soup was consumed either unchanged (Control) or with added MSG. The addition of MSG during training increased both pleasantness and savory character of the soup and resulted in a larger increase in rated pleasantness of the soup in the MSG-trained relative to control condition when the soup was re-evaluated Post-training without MSG. There was also a significant increase in voluntary soup intake Post-training after the soup had been paired with MSG but not in the Control condition, and rated hunger increased more after tasting the soup Post-training in the MSG-trained but not Control condition. These findings demonstrate that co-experience of a savory flavor and MSG can result in increased subsequent liking and intake for the flavor in the absence of MSG, and possible explanations for how MSG reinforces learning are discussed

The Effects of Oral Consumption of Selenium Nanoparticles on Chemotactic and Respiratory Burst Activities of Neutrophils in Comparison with Sodium Selenite in Sheep

The present study was designed to compare the effects of nano-selenium and of sodium selenite on the chemotactic and respiratory burst activities of neutrophils in sheep. Fifteen sheep were randomly divided into three groups. Groups 1 and 2 received selenium nanoparticles (1 mg/kg) or sodium selenite (1 mg/kg) orally, respectively, for ten consecutive days, and the third group was considered as the control. To determine the chemotactic and respiratory burst activities of the neutrophils, the leading front assay and the NBT test were used on heparinized blood samples that were collected at different intervals (days 0, 10th, 20th, and 30th). The results obtained showed that the chemotactic activities in groups 1 and 2 increased significantly on the 10th, 20th, and 30th day, compared to day 0, and on the 20th day in comparison with the 10th day, while in group 2, there was a significant decrease on the 30th day compared to the 20th day. The chemotactic activities in group 1 were significantly higher than in group 2 on the 10th day and in the control group on the 10th, 20th, and 30th day, but the chemotactic activities in group 2 were significantly higher than those in the control group only on the 20th day. On the 30th day into the experiment, the respiratory bursts in groups 1 and 2 were significantly stronger in comparison with those at day 0. Overall, nano-selenium increased the chemotactic and respiratory burst activities more significantly than sodium selenite, which is suggestive of a stronger stimulatory effect of the Se nanoparticles on intracellular activities

Comparative Effectiveness of Tumor Response Assessment Methods: Standard of Care Versus Computer-Assisted Response Evaluation

Purpose To compare the effectiveness of metastatic tumor response evaluation with computed tomography using computer-assisted versus manual methods. Materials and Methods In this institutional review board–approved, Health Insurance Portability and Accountability Act–compliant retrospective study, 11 readers from 10 different institutions independently categorized tumor response according to three different therapeutic response criteria by using paired baseline and initial post-therapy computed tomography studies from 20 randomly selected patients with metastatic renal cell carcinoma who were treated with sunitinib as part of a completed phase III multi-institutional study. Images were evaluated with a manual tumor response evaluation method (standard of care) and with computer-assisted response evaluation (CARE) that included stepwise guidance, interactive error identification and correction methods, automated tumor metric extraction, calculations, response categorization, and data and image archiving. A crossover design, patient randomization, and 2-week washout period were used to reduce recall bias. Comparative effectiveness metrics included error rate and mean patient evaluation time. Results The standard-of-care method, on average, was associated with one or more errors in 30.5% (6.1 of 20) of patients, whereas CARE had a 0.0% (0.0 of 20) error rate (P < .001). The most common errors were related to data transfer and arithmetic calculation. In patients with errors, the median number of error types was 1 (range, 1 to 3). Mean patient evaluation time with CARE was twice as fast as the standard-of-care method (6.4 minutes v 13.1 minutes; P < .001). Conclusion CARE reduced errors and time of evaluation, which indicated better overall effectiveness than manual tumor response evaluation methods that are the current standard of care