Simultaneous selection in beans for stability and high agronomic performance.

The objective of this study was to select common bean cultivars based on their stability for flowering, cycle, insertion of the first pod, grain yield, and high agronomic performance. Twenty experiments were carried out between 2000 and 2014, during two growing seasons, in Rio Grande do Sul, Brazil. The Eberhart and Russel, and Lin and Binns methods, as well as the additive main effect and multiplicative interaction (AMMI) method, were used to evaluate the stability of flowering, cycle, insertion of the first pod, and grain yield of 10 common cultivars in all experiments. The Eberhart and Russel, Lin and Binns, and AMMI methods identified the Carioca cultivar as the most stable for insertion of the first pod, and the Iraí cultivar as the most instable for flowering and cycle. The Pérola cultivar shows stability for flowering, cycle, and insertion of the first pod, and Guapo Brilhante is stable for grain yield, according to the Lin and Binns method. Controlled crossing between Pérola and Guapo Brilhante is recommended for the development of new common bean cultivars with greater stability for semi-early cycle, architecture of upright plant, and grain yield.

High nitrogen removal rate using ANAMMOX process at short hydraulic retention time.

The anaerobic ammonium oxidation (ANAMMOX) is a chemolithoautotrophic process, which converts NH(4)(+) to N(2) using nitrite (NO(2)(-)) as the electron acceptor. This process has very high nitrogen removal rates (NRRs) and is an alternative to classical nitrification/denitrification wastewater treatment. In the present work, a strategy for nitrogen removal using ANAMMOX process was tested evaluating their performance when submitted to high loading rates and very short hydraulic retention times (HRTs). An up-flow ANAMMOX column reactor was inoculated with 30% biomass (v v(-1)) fed from 100 to 200 mg L(-1) of total N (NO(2)(-)-N + NH(4)(+)-N) at 35 °C. After start-up and process stability the maximum NRR in the up-flow anaerobic sludge blanket (UASB) reactor was 18.3 g-N L(-1) d(-1) operated at 0.2 h of HRT. FISH (fluorescence in situ hybridization) analysis and process stoichiometry confirmed that ANAMMOX was the prevalent process for nitrogen removal during the experiments. The results point out that high NRRs can be obtained at very short HRTs using up-flow ANAMMOX column reactor configuration.

Integrin-mediated drug delivery in cancer and cardiovascular diseases with peptide-functionalized nanoparticles.

In recent years progress has been speeding in studies of cell-cell interaction governed by adhesion molecules, and in particular by integrins and their ligands in cells and in the extracellular matrix. Integrins are distributed in a variety of tissues and blood cells. An increased expression of integrins and of their adhesion counterparts is often observed in sites relevant to disease states. Important roles are played by integrin α(v)ß(3) in cancer angiogenesis and metastatic diffusion, in angiogenesis in ischemic tissues, in atherosclerotic damage and restenosis, and in osteoporosis; by integrin α(5)ß(1) in angiogenesis processes; by integrin α(II)bß(3), mediating adhesion of platelets to fibrinogen, in thrombotic conditions; by integrins α(4)ß(1) and α(L)ß(2) in inflammatory conditions, particularly autoimmune diseases and asthma. Therefore, medicinal chemists became attracted and engaged in research on integrins as therapeutic and diagnostic targets. Many efforts have been directed towards the development of molecular constructs including integrin ligands that can provide advanced tools for drug delivery, for imaging, or for their combination (theranostics), particularly by exploiting the new possibilities offered by nanoparticles. Here we will review the current status and the future perspective of integrin targeting of several kind of nanoparticles, going from most studied micelles, liposomes, polymeric nanoparticles to finish with inorganic nanoparticles of more recent employment. Perfluoroalkane filled microbubbles, although over the nanometric size (1-10 µm) will be shortly considered.

The pulmonary pharmacology of [4-methoxy-N1-(4-trans-nitrooxycyclohexyl)-N3-(3-pyridinylmethyl)-1,3-benzenedicarboxamide] (2NTX-99), an anti-atherotrombotic compound with therapeutic potential in pathological conditions that target lung vasculature.

The pharmacological activity of 2NTX-99 ([4-methoxy-N1-(4-trans-nitrooxycyclohexyl)-N3-(3-pyridinylmethyl)-1,3-benzenedicarboxamide]) was investigated in vitro in the intact, rat pulmonary vasculature and in guinea pig airways. Rat lungs were perfused at constant flow and changes in vascular tone recorded. Challenge with the TXA2 analogue 9,11-dideoxy-9α11α-methanoepoxy ProstaglandinF2 (U46619, 0.5 µM) increased vessel tone (32.48±1.5 vs 13.13±0.56 mmHg; n=12). 2NTX-99 (0.1-100 µM; n=5), caused a concentration-dependent relaxation, prevented by 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 10 µM, n=4), an inhibitor of soluble guanylate cyclase. Acetylcholine (0.1-10 µM; n=3) and a reference NO-donor, isosorbide-5-mononitrate (5-100 µM; n=4), were ineffective. Intraluminal perfusion of washed human platelets (2 × 108 cells/ml) increased intravascular pressure after challenge with arachidonic acid (AA, 2 µM; n=5), an increase abolished by acetylsalicylic acid and significantly reduced by 2NTX-99 (40 µM; n=5). TXB2 in the lung perfusate was detected after platelet activation, 2NTX-99 inhibited TXA2 synthesis (6.45±0.6 and 1.10±0.2 ng/ml, respectively). 2NTX-99 did not alter central or peripheral airway responsiveness to Histamine (0.001-300 µM; n=6), U46619 (0.001-3 µM, n=3) or LTD4 (1 pM-1 µM; n=6). 2NTX-99 vasodilates the pulmonary vasculature via the release of nitric oxide (NO) and reduces intraluminal, AA-induced, TXA2 formation. The combined activity of 2NTX-99 as an NO-donor and a TXA2-synthesis inhibitor provides strong support for its potential therapeutic use in pathologies of the pulmonary vascular bed (e.g. pulmonary hypertension).

Inventory of experiences from national/regional dietary monitoring surveys using EPIC-Soft.

BACKGROUND/OBJECTIVES: The EPIC-Soft 24-h recall (the software developed to conduct 24-h dietary recalls (24-HDRs) in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study) has been used in several regional/national dietary monitoring surveys. The main objective of the study was to present and discuss design, settings, logistics, data management and quality controls of dietary monitoring surveys that used EPIC-Soft for the collection of food consumption data. SUBJECTS/METHODS: Within European Food Consumption Validation (EFCOVAL), a questionnaire including questions on current/past EPIC-Soft experiences and requirements for the future was developed and sent to all institutes that used EPIC-Soft in their food consumption survey(s) (five surveys in four different countries). RESULTS: EPIC-Soft was used in the national food consumption survey in Belgium (≥ 15-97 years), Germany (14-80 years), the Netherlands (19-30 years and 2-6 years) and Spain (regional only; 4-18 years). Participation rates in these surveys were 46% (Belgium), 42% (Germany), 42% (Dutch survey in adults), 79% (Dutch survey in children) and 77% (Basque survey). Two 24-HDRs were collected by conducting face-to-face interviews in Belgium and Spain, and through telephone interviews in Germany and the Netherlands. Except the Netherlands (19-30 years), where the study was conducted only in autumn, in all other countries the study was conducted throughout the four seasons, including all days of the week. Interviews were conducted by dietitians, except in Germany and Spain. Mean EPIC-Soft interview time was 20-34 min. The dropout rate between the first and second interviews was low (<7.5%) in all surveys. CONCLUSION: EPIC-Soft has been used in different study settings and populations for nutritional exposure assessments. To guarantee the comparability of data across countries, recommendations for the design of future pan-European dietary monitoring surveys using EPIC-Soft should be drawn.

Respondents' evaluation of the 24-h dietary recall method (EPIC-Soft) in the EFCOVAL Project.

BACKGROUND: To improve participation rate, accuracy and respondents' compliance, it is important to know the respondents' viewpoint. OBJECTIVE: To evaluate respondents' preferences and perception about the EPIC-Soft (the software developed to conduct 24-h dietary recalls (24-HDRs) in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study) 24-HDR interviews and to compare these preferences and perception between population groups (for example, between genders). DESIGN: Data were collected in Belgium, Czech Republic, France, the Netherlands and Norway in 2007. Two 24-HDRs (face-to-face and telephone administered) were conducted using EPIC-Soft. An evaluation questionnaire on different study aspects was completed by the respondents. SETTING: Data were collected in the European Food Consumption Validation Study. SUBJECTS: A convenience sample of 600 apparently healthy men and women, 45-65 years old and including all educational levels, were recruited (120 subjects per country). Differences among population groups were compared by means of the χ (2)-test. RESULTS: A total of 585 respondents completed the evaluation questionnaire. In all, 88% experienced problems only to a low degree when answering face-to-face and telephone-administered 24-HDR using EPIC-Soft. A total of 15% would have preferred help of another person during the face-to-face interview in the study center (mainly men: P < 0.001). Significantly, more subjects in the Netherlands and in Norway preferred two telephone (instead of face-to-face) interviews compared with the other countries (P<0.001). CONCLUSION: Most subjects only experienced problems to a low degree during the EPIC-Soft interviews. Differences in preferences and capabilities to answer the EPIC-Soft interviews were identified between population groups (for example, gender differences). Therefore, the methods and the design to be used in a survey should be adapted according to the study population, so as to optimize response rate and compliance.

Potential and requirements for a standardized pan-European food consumption survey using the EPIC-Soft software.

BACKGROUND/OBJECTIVES: To describe the strengths, limitations and requirements of using EPIC-Soft software (the software developed to conduct 24-h dietary recalls in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study) in pan-European food consumption surveys, and to discuss potentials and barriers for a harmonized pan-European food consumption survey. SUBJECTS/METHODS: The paper is based on the experiences in the 'European Food Consumption and Validation' Project, which included updating six existing and preparing one new country-specific EPIC-Soft version, applying EPIC-Soft in validation and feasibility studies, and estimating the intake of nutrients and flavoring substances. The experiences were discussed in the September 2009 workshop 'Pan-European Food Consumption Surveys--for Standardized and Comparable Transnational Data Collection'. RESULTS: EPIC-Soft is suitable for detailed and standardized food consumption data collection in pan-European food consumption surveys. A thorough preparation of all aspects of the food consumption survey is important for the quality and efficiency during data collection and processing. The preparation and data-handling phase of working with EPIC-Soft is labor intensive and requires trained, motivated and qualified personnel. CONCLUSIONS: Given the suitability of EPIC-Soft as standardized dietary assessment tool in European dietary monitoring, the proposed strategy toward a pan-European food consumption survey is to prepare well, to allow flexibility in national extensions and to start with a limited number of countries that are interested.

The standardized computerized 24-h dietary recall method EPIC-Soft adapted for pan-European dietary monitoring.

BACKGROUND/OBJECTIVES: The EPIC-Soft program (the software initially developed to conduct 24-h dietary recalls (24-HDRs) in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study) was recommended as the best way to standardize 24-HDRs for future pan-European dietary monitoring. Within European Food Consumption Validation (EFCOVAL), EPIC-Soft was adapted and further developed on various aspects that were required to optimize its use. In this paper, we present the structure and main interview steps of the EPIC-Soft program, after implementation of a series of new specifications deemed to satisfy specific requirements of pan-European monitoring surveys and other international studies. SUBJECTS/METHODS: Updates to optimize the EPIC-Soft program were ascertained according to the following stepwise approach: (1) identification of requested specifications to be potentially implemented through an ad hoc 'EPIC-Soft specifications questionnaire' sent to past, current and possible future users of the software; (2) evaluation of the specifications in collaboration with two ad hoc task force groups and through a workshop; (3) development of a technical solution for each retained specification; (4) implementation of the specifications by software developers; (5) testing and amendment of bugs. RESULTS: A number of new specifications and facilities were implemented to EPIC-Soft program. In addition, the software underwent a full reprogramming and migration to a modern Windows environment, including changes in its internal architecture and user interface. Although the overall concept and structure of the initial software were not changed substantially, these improvements ease the current and future use of EPIC-Soft and increase further its adaptation to other countries and study contexts. CONCLUSIONS: EPIC-Soft is enriched with further functions and facilities expected to fulfil specific needs of pan-European dietary monitoring and risk assessment purposes. The validity, feasibility and relevance of this software for different national and international study designs, and the logistical aspects related to its implementation are reported elsewhere.

Contribution of highly industrially processed foods to the nutrient intakes and patterns of middle-aged populations in the European Prospective Investigation into Cancer and Nutrition study.

OBJECTIVES: To describe the contribution of highly processed foods to total diet, nutrient intakes and patterns among 27 redefined centres in the 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Single 24-hour dietary recalls were collected from 36,034 individuals (aged 35-74 years) using a standardized computerized interview programme (EPIC-SOFT). Centre-specific mean food intakes (g/day) were computed according to their degree of food processing (that is, highly, moderately and non-processed foods) using a specifically designed classification system. The contribution (%) of highly processed foods to the centre mean intakes of diet and 26 nutrients (including energy) was estimated using a standardized nutrient database (ENDB). The effect of different possible confounders was also investigated. RESULTS: Highly processed foods were an important source of the nutrients considered, contributing between 61% (Spain) and 78-79% (the Netherlands and Germany) of mean energy intakes. Only two nutrients, beta-carotene (34-46%) and vitamin C (28-36%), had a contribution from highly processed foods below 50% in Nordic countries, in Germany, the Netherlands and the United Kingdom, whereas for the other nutrients, the contribution varied from 50 to 91% (excluding alcohol). In southern countries (Greece, Spain, Italy and France), the overall contribution of highly processed foods to nutrient intakes was lower and consisted largely of staple or basic foods (for example, bread, pasta/rice, milk, vegetable oils), whereas highly processed foods such as crisp bread, breakfast cereals, margarine and other commercial foods contributed more in Nordic and central European centres. CONCLUSIONS: Highly industrially processed foods dominate diets and nutrient patterns in Nordic and central European countries. The greater variations observed within southern countries may reflect both a larger contribution of non/moderately processed staple foods along with a move from traditional to more industrialized dietary patterns.

Use of dietary supplements in the European Prospective Investigation into Cancer and Nutrition calibration study.

BACKGROUND: Dietary supplement use is increasing, but there are few comparable data on supplement intakes and how they affect the nutrition and health of European consumers. The aim of this study was to describe the use of dietary supplements in subsamples of the 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Specific questions on dietary supplement use were asked as a part of single 24-h recalls performed on 36,034 men and women aged 35-74 years from 1995 to 2000. RESULTS: Between countries, the mean percentage of dietary supplement use varied almost 10-fold among women and even more among men. There was a clear north-south gradient in use, with a higher consumption in northern countries. The lowest crude mean percentage of use was found in Greece (2.0% among men, 6.7% among women), and the highest was in Denmark (51.0% among men, 65.8% among women). Use was higher in women than in men. Vitamins, minerals or combinations of them were the predominant types of supplements reported, but there were striking differences between countries. CONCLUSIONS: This study indicates that there are wide variations in supplement use in Europe, which may affect individual and population nutrient intakes. The results underline the need to monitor consumption of dietary supplements in Europe, as well as to evaluate the risks and benefits.

The EPIC nutrient database project (ENDB): a first attempt to standardize nutrient databases across the 10 European countries participating in the EPIC study.

OBJECTIVE: This paper describes the ad hoc methodological concepts and procedures developed to improve the comparability of Nutrient databases (NDBs) across the 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). This was required because there is currently no European reference NDB available. DESIGN: A large network involving national compilers, nutritionists and experts on food chemistry and computer science was set up for the 'EPIC Nutrient DataBase' (ENDB) project. A total of 550-1500 foods derived from about 37,000 standardized EPIC 24-h dietary recalls (24-HDRS) were matched as closely as possible to foods available in the 10 national NDBs. The resulting national data sets (NDS) were then successively documented, standardized and evaluated according to common guidelines and using a DataBase Management System specifically designed for this project. The nutrient values of foods unavailable or not readily available in NDSs were approximated by recipe calculation, weighted averaging or adjustment for weight changes and vitamin/mineral losses, using common algorithms. RESULTS: The final ENDB contains about 550-1500 foods depending on the country and 26 common components. Each component value was documented and standardized for unit, mode of expression, definition and chemical method of analysis, as far as possible. Furthermore, the overall completeness of NDSs was improved (>or=99%), particularly for beta-carotene and vitamin E. CONCLUSION: The ENDB constitutes a first real attempt to improve the comparability of NDBs across European countries. This methodological work will provide a useful tool for nutritional research as well as end-user recommendations to improve NDBs in the future.

Body mass index, waist circumference and waist-hip ratio and serum levels of IGF-I and IGFBP-3 in European women.

OBJECTIVE: To examine the relationship between body mass index (BMI) and waist-hip ratio (WHR) with serum levels of insulin-like growth factor-I (IGF-I), and its binding protein (IGFBP)-3. DESIGN: Cross-sectional study on 2139 women participating in a case-control study on breast cancer and endogenous hormones. Data on lifestyle and reproductive factors were collected by means of questionnaires. Body height, weight, waist and hip circumferences were measured. Serum levels of IGF-I and insulin-like binding protein (IGFBP)-3 were measured by enzyme-linked immunosorbent assays. Adjusted mean levels of IGF-I and IGFBP-3 across quintiles of BMI, waist circumference, and WHR were calculated by linear regression. Results were adjusted for potential confounders associated with IGF-I and IGFBP-3. RESULTS: Adjusted mean serum IGF-I values were lower in women with BMI<22.5 kg/m(2) or BMI>29.2 kg/m(2) compared to women with BMI within this range (P(heterogeneity)<0.0001, P(trend)=0.35). Insulin-like growth factor-I was not related to WHR after adjustment for BMI. IGF-binding protein-3 was linearly positively related to waist and WHR after mutual adjustment. The molar ratio IGF-I/IGFBP-3 had a non-linear relation with BMI and a linear inverse relationship with WHR (P (trend)=0.005). CONCLUSIONS: Our data confirm the nonlinear relationship of circulating IGF-I to total adiposity in women. Serum IGFBP-3 was positively related to central adiposity. These suggest that bioavailable IGF-I levels could be lower in obese compared to non-obese women and inversely related to central adiposity.

European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection.

The European Prospective Investigation into Cancer and Nutrition (EPIC) is an ongoing multi-centre prospective cohort study designed to investigate the relationship between nutrition and cancer, with the potential for studying other diseases as well. The study currently includes 519 978 participants (366 521 women and 153 457 men, mostly aged 35-70 years) in 23 centres located in 10 European countries, to be followed for cancer incidence and cause-specific mortality for several decades. At enrollment, which took place between 1992 and 2000 at each of the different centres, information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire addressing usual diet. Anthropometric measurements were performed and blood samples taken, from which plasma, serum, red cells and buffy coat fractions were separated and aliquoted for long-term storage, mostly in liquid nitrogen. To calibrate dietary measurements, a standardised, computer-assisted 24-hour dietary recall was implemented at each centre on stratified random samples of the participants, for a total of 36 900 subjects. EPIC represents the largest single resource available today world-wide for prospective investigations on the aetiology of cancers (and other diseases) that can integrate questionnaire data on lifestyle and diet, biomarkers of diet and of endogenous metabolism (e.g. hormones and growth factors) and genetic polymorphisms. First results of case-control studies nested within the cohort are expected early in 2003. The present paper provides a description of the EPIC study, with the aim of simplifying reference to it in future papers reporting substantive or methodological studies carried out in the EPIC cohort.

European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study: rationale, design and population characteristics.

The European Prospective Investigation into Cancer and Nutrition (EPIC), which covers a large cohort of half a million men and women from 23 European centres in 10 Western European countries, was designed to study the relationship between diet and the risk of chronic diseases, particularly cancer. Information on usual individual dietary intake was assessed using different validated dietary assessment methods across participating countries. In order to adjust for possible systematic over- or underestimation in dietary intake measurements and correct for attenuation bias in relative risk estimates, a calibration approach was developed. This approach involved an additional dietary assessment common across study populations to re-express individual dietary intakes according to the same reference scale. A single 24-hour diet recall was therefore collected, as the EPIC reference calibration method, from a stratified random sample of 36 900 subjects from the entire EPIC cohort, using a software program (EPIC-SOFT) specifically designed to standardise the dietary measurements across study populations. This paper describes the design and populations of the calibration sub-studies set up in the EPIC centres. In addition, to assess whether the calibration sub-samples were representative of the entire group of EPIC cohorts, a series of subjects' characteristics known possibly to influence dietary intakes was compared in both population groups. This was the first time that calibration sub-studies had been set up in a large multi-centre European study. These studies showed that, despite certain inherent methodological and logistic constraints, a study design such as this one works relatively well in practice. The average response in the calibration study was 78.3% and ranged from 46.5% to 92.5%. The calibration population differed slightly from the overall cohort but the differences were small for most characteristics and centres. The overall results suggest that, after adjustment for age, dietary intakes estimated from calibration samples can reasonably be interpreted as representative of the main cohorts in most of the EPIC centres.

Consumption of vegetables, fruit and other plant foods in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts from 10 European countries.

OBJECTIVE: To describe and compare the consumption of the main groups and sub-groups of vegetables and fruits (V&F) in men and women from the centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: Cross-sectional analysis. Dietary intake was assessed by means of a 24-hour dietary recall using computerised interview software and standardised procedures. Crude and adjusted means were computed for the main groups and sub-groups of V&F by centre, separately for men and women. Adjusted means by season, day of the week and age were estimated using weights and covariance analysis. SETTING: Twenty-seven centres in 10 European countries participating in the EPIC project. SUBJECTS: In total, 35 955 subjects (13 031 men and 22 924 women), aged 35-74 years, randomly selected from each EPIC cohort. RESULTS: The centres from southern countries had the highest consumption of V&F, while the lowest intake was seen in The Netherlands and Scandinavia for both genders. These differences were more evident for fruits, particularly citrus. However, slightly different patterns arose for some sub-groups of vegetables, such as root vegetables and cabbage. Adjustment for body mass index, physical activity, smoking habits and education did not substantially modify the mean intakes of vegetables and fruits. CONCLUSIONS: Total vegetable and fruit intake follows a south-north gradient in both genders, whereas for several sub-groups of vegetables a different geographic distribution exists. Differences in mean intake of V&F by centre were not explained by lifestyle factors associated with V&F intake.

Minimally invasive facial rejuvenation endolaser mid-face lift.

Endolaser mid-face lift was performed on patients in a multi-center study over a 36-month period (Feb. 1998 to Feb. 2001). It permits significant facial rejuvenation through small incisions. This technique achieves aesthetic results and wider rejuvenation while being less traumatic and creating minimal morbidity. Combined with other procedures, it rejuvenates the face by three strategic methods: soft tissue suspension, reversal of photo aging, and correction of the depletion of volume. To achieve this triple result, the mid-face lift is performed by endoscopic approach, and in every case is combined with the endoscopic lift of the frontal area. Laser resurfacing was used to reverse skin photo damage. The Ultrapulse CO2 laser and/or the Ultrafine Erbium YAG(Coherent, Inc, Palo Alto, CA) were used. The third combined procedure was the introduction of fat graft to compensate the atrophy/ptosis of fat and the depletion of bone mass (other filling materials besides fat may be used, depending on the preference of the surgeon). Our method of fixation using the Casagrande Needle (an evolution of Reverdin Needle) makes the mechanical purchase on the tissues to be suspended much easier, permitting the intra-oral and/or infra-orbital incisions to be eliminated. The present study of the technical evolution of the endolaser mid-face lift method allows us to conclude that a very satisfactory outcome has been reached, offering patients a minimally invasive procedure, which can be performed under local anesthesia, with low morbidity, imperceptible incisions, and an excellent long-term result.

Precursor RNAs harboring nonsense codons accumulate near the site of transcription.

Messenger RNAs containing premature termination codons (PTCs) are selectively eliminated by nonsense-mediated mRNA decay (NMD). Paradoxically, although cytoplasmic ribosomes are the only known species capable of PTC recognition, in mammals many PTC-containing mRNAs are apparently eliminated prior to release from the nucleus. To determine whether PTCs can influence events within the nucleus proper, we studied the immunoglobulin (Ig)-mu and T cell receptor (TCR)-beta genes using fluorescent in situ hybridization (FISH). Alleles containing PTCs, but not those containing a missense mutation or a frameshift followed by frame-correcting mutations, exhibited elevated levels of pre-mRNA, which accumulated at or near the site of transcription. Our data indicate that mRNA reading frame can influence events at or near the site of gene transcription.

Picotamide, an antithromboxane agent, inhibits the migration and proliferation of arterial myocytes.

Picotamide is an antiplatelet drug with a peculiar dual mechanism of action: it inhibits thromboxane A2 synthase and antagonizes the pharmacological responses mediated by thromboxane A2 receptor. We investigated the in vitro effect of picotamide on smooth muscle cell migration and proliferation. Picotamide (1-500 microM) decreased human and rat smooth muscle cell proliferation, evaluated as cell number, in a concentration-dependent and reversible manner. Picotamide inhibited DNA synthesis induced by fetal calf serum (10%), platelet-derived growth factor (PDGF-BB (20 ng/ml)), epidermal growth factor (EGF (1 nM)) and (15S)-hydroxy-11,9-(epoxymethano)prosta-5Z,13E-dienoic acid (U46619 (10 microM, thromboxane A2 receptor agonist)). Co-incubation of U46619 together with EGF or PDGF-BB resulted in a marked amplification of [3H]thymidine incorporation that was completely reversed by picotamide. The drug also inhibited smooth muscle cell migration induced by fibrinogen (600 microg/ml) or PDGF-BB (20 ng/ml) in a concentration-dependent manner. The ability of picotamide to interfere with myocyte migration and proliferation confers, at least in vitro, a pharmacological interest on the compound in atherogenesis.

Reproducibility of a food frequency questionnaire used in the New York University Women's Health Study: effect of self-selection by study subjects.

OBJECTIVE: The aim of the study was to investigate the reproducibility of a food frequency questionnaire (FFQ) used in a cohort of 14,290 women enrolled in the NYU Women's Health Study. DESIGN: A subset of 474 cohort subjects who completed the dietary questionnaire at baseline (FFQ-1) were approached again on the occasion of a second visit to the mammography study centre and asked to complete the questionnaire a second time (FFQ-2) two to four years after FFQ-1. Two to three months later the questionnaire was mailed to the subjects, and they were asked to complete it a third time (FFQ-3). SETTING: A breast cancer screening clinic. SUBJECTS: Of the 474 subjects selected, 100% completed the second questionnaire while only 56% completed and mailed back FFQ-3. This made it possible to compare the long-term reproducibility of dietary intake measurements and baseline dietary habits between the two groups of subjects 'respondents', who agreed to complete the questionnaire a third time, and 'non-respondents', who did not. RESULTS: Among respondents (56% of study subjects), energy-adjusted correlation coefficients for short-term reproducibility between FFQ-2 and FFQ-3 ranged from 0.50-0.64 for nutrients, and from 0.44-0.67 for foods. The long-term reproducibility was lower, ranging from 0.36-0.53 for nutrients, and from 0.31-0.48 for specific food groups. Among those who did not respond to FFQ-3, crude correlations for long-term reproducibility, unadjusted for energy intake, were generally lower than among respondents. Nevertheless, after adjustment for energy intake, correlations for long-term reproducibility (FFQ-2 to FFQ-1) were of similar magnitude in both groups. In addition, 'non-respondents' reported lower intake of fruit and vegetables and higher intake of meat. CONCLUSIONS: The results of this study suggest that subjects who volunteer to participate in substudies on the validity or reproducibility of dietary questionnaire measurements may tend to provide more accurate responses to the questionnaire. The phenomenon seems related more to accuracy of reporting of absolute intake levels than of the relative composition of diet, self-selection may be associated with differences in dietary habits.

[Treatment of femoral false aneurysms following cardiac catheterization with compression and color Doppler echocardiography monitoring]. / Tratamento de falsos-aneurismas femorais pós-cateterismo cardíaco pela compressão com monitorização pelo ecodoppler a cores.

PURPOSE: To evaluate the efficiency of a non-surgical treatment of the femoral false aneurysm following cardiac catheterization using the color Doppler echocardiography monitorization. METHODS: From August 1993 to October 1996, 17 patients were evaluated by the color Doppler echocardiography, 7 women and 10 men, between 58 and 77 years of age, with the diagnosis of femoral false aneurysms after cardiac catheterization. All the cases were selected for therapy with this new technique, that consisted of the compression of the false aneurysm with the transducer of the ultrasound device and monitorization of the evolution of the false aneurysm thrombosis, through image observation in real time, on the equipment monitor. RESULTS: There were 17 selected patients, 16 were successfully treated, requiring an average of 30 minutes of compression with consequent thrombosis of the false aneurysm, without recurrence in 30 days of follow-up. No complications with the use of this technique were noted and the hospitalization period was, on average, 1 day. CONCLUSION: This technique is efficient, safe and should be the first choice for the therapy of patients with femoral aneurysm following cardiac catheterization.