However, we did not find any significant correlations between PFOS concentration in maternal and cord blood samples and age bracket, birth weight, or levels of thyroid-stimulating hormone or free thyroxine. Our study revealed that human fetuses in Japan may be exposed to relatively high levels of FOCs. Further investigation is required to determine the postnatal effects of fetal exposure to FOCs.Fluorinated organic compounds (FOCs), such as perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorooctane sulfonylamide (PFOSA), are widely used in the manufacture of plastic, electronics, textile, and construction material in the apparel, leather, and upholstery industries. FOCs have been detected in human blood samples. Studies have indicated that FOCs may be detrimental to rodent development possibly by affecting thyroid hormone levels. In the present study, we determined the concentrations of FOCs in maternal and cord blood samples. Pregnant women 17–37 years of age were enrolled as subjects. FOCs in 15 pairs of maternal and cord blood samples were analyzed by liquid chromatography–electrospray mass spectrometry coupled with online extraction. The limits of quantification of PFOS, PFOA, and PFOSA in human plasma or serum were 0.5, 0.5, and 1.0 ng/mL, respectively. The method enables the precise determination of FOCs and can be applied to the detection of FOCs in human blood samples for monitoring human exposure. PFOS concentrations in maternal samples ranged from 4.9 to 17.6 ng/mL, whereas those in fetal samples ranged from 1.6 to 5.3 ng/mL. In contrast, PFOSA was not detected in fetal or maternal samples, whereas PFOA was detected only in maternal samples . Our results revealed a high correlation between PFOS concentrations in maternal and cord blood ( Fluorinated organic compounds (FOCs), such as perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorooctane sulfonylamide (PFOSA), are stable chemicals with a wide range of industrial and consumer applications . Recent In the United States, PFOS is a stable FOC with many industrial applications. The amount of PFOS used in consumer application totals 5.6 million lb . These fPFOA is widely used in the production of chemicals and in aircraft and electronic products manufacturing. PFOA does not appear to be biomagnified in animals. However, it is a persistent pollutant, and low concentrations are detected in human blood, according to a risk assessment study . In the Because of the ubiquity of FOCs and their potential role in increasing the risk of neuroendocrine and reproductive dysfunction, human exposure assessment studies are urgently needed. A quantitative analysis of four FOCs in 65 human serum samples collected from several biologic supply companies in the United States detected PFOS (6.7–81.5 ng/mL), PFOA , and PFOSA  . A studyThe aim of the present study was to determine human cord and maternal serum concentrations of PFOS, PFOA, and PFOSA for fetal risk assessment. Although based on only a small sample set, our findings indicate the levels of FOCs to which Japanese women are exposed. We developed an easy, reliable, and high-throughput analytical method that uses liquid chromatography–electrospray mass spectrometry (LC-MS) coupled with online extraction to measure specific FOCs in human plasma and serum samples. This method enables the precise determination of standards in human blood samples and can be applied to the detection of PFOS, PFOA, and PFOSA in human blood samples for monitoring human exposure.n = 15; We recruited subjects between February and July 2003 at Sapporo Toho Hospitals in Hokkaido, Japan. This study was conducted with all the subjects’ written informed consent and was approved by the institutional ethical board for epidemiologic studies at the Hokkaido University Graduate School of Medicine. The data of physical and biologic examinations, laboratory tests, and questionnaires were recorded by the Department of Public Heath, Hokkaido University Graduate School of Medicine. Blood was sampled from pregnant women n = 15;  between PFOS , PFOA , and PFOSA  were purchased from Wako Pure Chemical Inc. , Fluka Chemie AG , and ABCR GmbH & Co. . The internal standard (perfluorodecanoic acid) was purchased from Lancaster Company, Inc. . Other reagents and solvents were of HPLC grade and were purchased from Wako Pure Chemical Inc. . The distilled water purification system was Milli-Q gradient A 10 with an EDS polisher .8–3  with a Mightysil RP-18 GP precolumn .LC-MS with electrospray ionization was performed using an Agilent 1100 MSD-SL system . The working conditions were as follows: The drying nitrogen gas temperature was set at 350°C and was introduced into the capillary region at a flow rate of 12 L/min; the capillary was held at a potential of 3,500 V relative to the counter electrode in the negative-ion mode for all compounds. The fragmenter voltages were 220 V for PFOS, 130 V for PFOA, and 170 V for PFOSA during the chromatographic run. The direct injection volume was 30 μL. The column used was Inertsil CThe column-switching LC-MS coupled with an on-line extraction system consisted of this LC-MS combined with an LC pump  and Oasis HLB extraction column . After a blood sample was injected by an autosampler, it was loaded onto the extraction column by flowing water/methanol  at a rate of 1.0 mL/min using a Shimadzu pump for 5 min. After on-line extraction for 5 min, the position of the switching valve was changed. This configuration connected the back-flashing extraction column to the analytical column and the MS detector in the flow path of the Agilent pump. After 20 min, the switching valve was returned to its original position. The run time for the assay of the sample mixture was 30 min. Gradient mobile phase of 1.0 mM ammonium acetate in water/acetonitrile (vol/vol) was used at a flow rate of 0.2 mL/min (5–15 min using a linear increase from 65 to 85% acetonitrile solution and holding at 85%).g for 10 min. The top clear layer was removed to the glass tube. This sample solution was filtered. This solution was analyzed by column-switching LC-MS. We analyzed quality-control materials (spiked samples in 25 ng/mL of PFOS) with each batch of samples on separated days. In the result, this material did not deviate from the 99% confidence interval (CI) .In the quantitative procedure, standard solutions of PFOS, PFOA, and PFOSA were prepared in aqueous solution to cover the calibration range. Quantitative analysis was performed in the single ion monitoring mode to maximize sensitivity. PFOS, PFOA, and PFOSA concentrations in each sample were calculated relative to the internal standard added to the sample before direct analysis. Calibration curves of PFOS, PFOA, and PFOSA were performed daily for all samples with internal standard. We added 0.3 mL of sample to 0.3 mL of internal standard solution. The mixed sample was centrifuged at 3,000 × 8 column and detected by MS in the selected ion monitoring mode. When working in the selected ion monitoring mode, the m/z ions for PFOS, PFOA, and PFOSA were [M–K]− 499, [M–COOH]− 369, and [M–H]− 498. In addition, the m/z ion of the internal standard was designated as [M–COOH]− 469 in the negative ion mode.The method was developed previously. The compounds were separated by reverse-phase LC with a CThe analysis of trace levels of PFOS, PFOA, and PFOSA in biologic samples is complicated by contamination, particularly by leaching from Teflon plastic. Thus, care must be taken to control contamination during experiments and, where possible, to eliminate the contamination. Investigations of PFOS, PFOA, and PFOSA contamination of the Milli-Q water system, the plastic tube, and the LC system produced negative results (below the limit of detection). We investigated whether the recoveries of PFOS, PFOA, and PFOSA (10 and 100 ng/mL) in the samples could be determined by this method. The average recoveries of PFOS, PFOA, and PFOSA ranged from 82.2 to 98.7%, with relative standard deviation < 5.2%. We used this method to assess FOC levels in human blood samples to obtain a reference range.4) levels of newborns were measured in Sapporo City Institute of Public Health. Blood specimens on filter paper were collected from infants between 4 and 7 days of age. TSH and free T4 were determined in single 0.3-cm disks punched from the same filter-paper blood. TSH and free T4 were measured using enzyme-linked immunosorbent assay . Detection limits were for TSH, 0.5 μIU/mL, and for free T4, 0.20 ng/dL, respectively.Thyroid-stimulating hormone (TSH) and free thyroxine   . The ave= 0.876) . On the To the best of our knowledge, this is the first report of PFOS and its related compounds in pregnant Japanese women and fetal cord blood. The issue of the bioavailability of PFOS in human, particularly in pregnant women and their cord blood, is controversial. A study of female human exposure levels of PFOS concentration found that levels in the United States are approximately twice those in Japan . In contOn the other hand, PFOA was detected in a small number of maternal samples but not in cord samples (< 0.1 ng/mL). PFOA may pose a developmental risk to children at concentrations already found in the blood of women and children, according to a U.S. EPA preliminary risk assessment released in April 2003 . Kannan in utero exposure to PFOS severely compromises postnatal survival of neonatal rats and mice and causes delays in growth and development accompanied by hypothyroxinemia in the surviving rat pups. However, little research has been conducted on the effects of PFOS on the human fetus, including epidemiologic, analytic, and toxicologic studies. It is necessary to investigate PFOS effects on thyroid hormone levels in a large number of fetuses. PFOS affects the estrous cycle and functions as an endocrine disruptor (4 are known to cause mental delay in humans. In the present study, there was no apparent association between fetal PFOS concentration and thyroid hormones; however, the sample size may have been too small to detect such a relationship in a human population. Large-scale follow-up studies are necessary to assess the adverse effects of exposure to PFOS and related compounds on fetal development. Further exposure assessment studies of PFOS in the susceptible population during pregnancy are needed to determine whether maternal exposure to PFOS can lead to adverse effects on the endocrine system in offspring. The description of a large-scale fetal population and the effects of PFOS on the endocrine system will be detailed in a forthcoming paper.Like polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers, PFOS may be able to cross the placental barrier to enter fetal circulation . Our datisruptor . Thyroid


This article systematically monitors the quality of life (QOL) of patients with schizophrenia from seven different sites across four European countries: France, Ireland, Portugal and Spain.A one-year prospective cohort study was carried out. Inclusion criteria for patients were: a clinical lifetime diagnosis of schizophrenia according to ICD-10 (F20) diagnostic criteria for research, age between 18 and 65 years and at least one contact with mental health services in 1993. Data concerning QOL were recorded in seven sites from four countries: France, Portugal, Ireland and Spain, and were obtained using the Baker and Intagliata scale. At baseline, 339 patients answered the QOL questionnaire. At one-year follow-up, Spain could not participate, so only 263 patients were contacted and 219 agreed to take part. QOL was compared across centres by areas and according to a global index. QOL was correlated with presence of clinical and social problems, needs for care and interventions provided during the one-year follow-up.We did not find any link between gender and QOL. There were some significant differences between centres concerning many items. What is more, these differences were relative: in Lisbon where the lowest level of satisfaction was recorded, people were satisfied with food but highly dissatisfied with finances, whereas in St Etienne, where the highest level of satisfaction was recorded, people were less satisfied with food when they were more satisfied with finances. The evolution in one year among those respondents who took part in the follow-up (excluding the subjects from Granada) showed different patterns depending on the items.The four countries have different resources and patients live in rather different conditions. However, the main differences as far as their QOL is concerned very much depend on extra-psychiatric variables, principally marital status and income. This article compares the quality of life of patients with schizophrenia in seven centres in four European countries: France , Ireland (Dublin), Portugal (Lisbon) and Spain (Granada), and relates this to social and clinical characteristics of patients within their different psychiatric systems.Indeed, there are large differences between these countries, mainly because of diverse historical backgrounds and the different resources made available for the care of patients with severe mental illness. In addition, the deinstitutionalization process has been implemented at various levels over the last twelve years in most European countries. Consequently, the ratio of psychiatric beds per 1,000 inhabitants remains high in some countries, whereas in others this ratio is low, either because of an effort to decrease it or because of a lack of availability. Moreover, alternatives to long-term hospitalisation such as sheltered housing are diversely developed, and in some countries the absence of such resources forces patients to live in their family's homes. The relationships between in-patient and out-patient care systems and the relationships between the psychiatric system and the primary care system vary substantially. As a result, continuity of care is ensured in varying degrees. It is also worth mentioning that social benefits for people suffering from severe psychiatric disorders vary greatly between countries, and are even totally lacking in some of them.The broad impact of this diversity on the lives of the severely and persistently mentally ill and the resulting completion of the needs generated by such illnesses pose a particular challenge in the assessment of services for these persons . RelevanBecause of this broad array of relevant outcomes and because of a prevailing concern that outcome assessments should include the patient's perspective, increased attention has been paid over the past decade to the development of patient "quality of life" measurements ,3. AssesA systematic comparison and evaluation of the QOL of patients and their one-year evolution across some European sites will then bring useful information for planning purpose.European Research Group On Schizophrenia (ERGOS).The present paper is based on a subset study on QOL conducted under the umbrella of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) version 1.0 [In the main study, the patients came from a network of researchers and clinicians in 10 centres, from seven countries: France , Germany (Mannheim), Ireland (Dublin), the Netherlands (Groningen), Portugal (Lisbon) and Spain (Granada). The study aimed to describe and compare the psychiatric care for a group of patients with chronic schizophrenia in a circumscribed geographical area in each participating country from Southern, Central and Northern Europe . This onsion 1.0 , which aThe results presented here concern a subset of seven centres from four countries: France, Portugal, Ireland and Spain, which agreed to collect additional data on QOL. As for the main study, the baseline assessment took place as soon as possible after a randomised selection from the list of eligible patients (those who had a lifelong diagnostic of schizophrenia assessed by SCAN) and after written informed consent following ethical committee recommendations. Finally, 419 patients constituted the target population . 38 (9.0%) could not be contacted any more after selection, and 45 (10.7%) refused to participate in the study. Then, another 29, who participated in the study, did not complete the QOL assessment. So, the final QOL assessment concerned 339 patients at baseline (80.9% participation rate). At one-year follow-up, Spain could not participate in the QOL assessment, so the remaining eligible patients were 263 and only 219 agreed to take part (83.3% of the baseline population).Satisfaction with Life Domains Scale (SLDS) [There are many QOL measures, which can be divided into generic and non generic. Since severe disorders are concerned we thought that a specific measure was needed and we selected the e (SLDS) ,21. ThisThe SLDS was initially developed to evaluate the impact of the Community Support Program in New York State on the QOL of chronically mentally ill patients. It is a self-report scale administered by a trained interviewer and takes approximately 10 minutes to administer. Its individual items cover 15 areas of everyday life: satisfaction with housing, neighbourhood, food, clothing, health, people lived with, friends, family, relations with other people, work/day schedule, spare time, leisure time, services and facilities in the area, economic situation, and place lived in now compared with state hospital. Respondents chose for each area one face from among seven proposed, corresponding to different emotional states. The faces varied from very satisfied and happy to not satisfied at all and sad. These can be summed into a total life satisfaction score.The SLDS has been extensively used with severe psychiatric patients in Belgium, Quebec and France. The French translation was available to us through a validation study conducted in Quebec . This stIt has to be noted that the initial 15-item version of the SLDS was modified by C. Mercier and P. Corten who deleted 1 item  and added 6 items covering love life, freedom and empowerment aspects. This modified version (20 items) was used by all centres except the Irish ones, which used the original 15-item version. Consequently, all results will be presented on the 14 common items for all centres, plus on the 6 added questions except for Dublin.For the patients who did not answer some of the items of the QOL questionnaire, we attributed the value 4  to the items in question in order to be able to compute the global score. Another solution would have been to use the mean or median value found for each item, however significance tests revealed that results would not have differed. For individual item comparisons, we are producing the number of patients by item.Past History and Sociodemographic Description schedule (PHSD) [The information concerning sociodemographic variables was collected by the e (PHSD) , which pNeeds For Care Assessment Schedule (NFCAS), a standardised procedure created by Brewin [The presence of a significant problem in various clinical and social domains was assessed at entry and followed up through the y Brewin ,25, whicy Brewin -28. A spy Brewin .The interview also covered 11 areas of clinical functioning  and 11 areas of social functioning .The Chi-square test, or the Fisher-exact test, whenever the number of cases was below 5, was used to compare ratios and the Student or Fisher test was used to compare means. In addition, multiple linear regression was used to measure the effect of variables on the level of global satisfaction. The software was SPSS V11 and Epi Info V6. Statistical significance was set at 0.05.Table Figure On average, levels of satisfaction for each area vary from 5.37 for food to 3.77 for finances. Between these extremes, the areas where people are most satisfied are clothing (5.11), housing (5.03), people they live with (5.02); then come family (4.92), neighbourhood (4.83), local services (4.79), relations with others (4.70) and friends (4.59), followed by work or day schedule (4.41), spare time (4.35), health (4.31) and leisure (4.26). If the six newly added items are considered, love life is the area where people are least satisfied (3.69), whereas the one where they are most satisfied is freedom (4.90), followed by responsibilities (4.65), self-confidence (4.41), life in general (4.24) and what other people think of you (4.21).However, there are some significant differences between centres concerning many items Figures  and 3. SWhen comparing variations of total QOL score according to the diverse sociodemographic characteristics for the entire sample at baseline, there are very few significant differences, and ones only relating to income source (p = 0.035): individuals who receive financial assistance from a partner (72.6) or their parents (68.9) are the most satisfied, followed by those who have a salary (67.8), then come those who receive unemployment benefit or social benefit (66.9), followed by those who receive disability benefits for sickness or handicap (65.7), which is the most frequent situation (129/329 cases). The persons least satisfied are those who receive their money for subsistence either from pensions (64.5), extended family or friends (60.7) and other sources of income (57.6).When individual satisfaction items are compared using various sociodemographic variables few are significant. First, one of these concerns age for satisfaction with finances only p = 0.046): the older respondents (> 35 years) are more satisfied than their younger counterparts (3.99 versus 3.56). Second, income is also linked to satisfaction in two areas: local services (p = 0.011) and finances (p = 0.008), those with the highest income being the most satisfied and those who have low income being dissatisfied. Source of income parallels this finding. Figure 6: the olThe evolution of the global QOL scores among those respondents who took part in the follow-up (excluding the subjects from Granada) is presented in Figure Sociodemographic and environmental variables appear to play a more important role at one-year follow-up than at baseline: with the time passing, their influence on various aspects of QOL increases.Women's global satisfaction increases (+5.39), whereas men change only slightly (+0.92) over time (p = 0.028). Respondents who are divorced or separated (+10.8) or cohabiting (+8.28) have the highest increase (p = 0.057). Those with the lowest income progress most (+4.58) whereas, in contrast, those with the highest income decline most . Globally, the main areas subject to change over time are finances, which gains one point in each centre, and family relationship, which looses more than one point. All remaining satisfaction areas slightly increase except that of love life which decreases.These evolutions are sometimes different by centres or according to some of the sociodemographic variables.Satisfaction with health increases over time in all centres, except La Verrière and St Etienne where it declines (p = 0.009). Relationship with the family deteriorates over time in varying degrees (p = 0.012) in each centre (the greatest deterioration occurring in La Verrière), whereas relationship with friends improves slightly, except in Lisbon (p = 0.038), and relationship with others improves slightly, except in St Etienne (p = 0.017). Leisure improves greatly in La Verrière and in Dublin and deteriorates in St Etienne (p = 0.002).Compared with men, women improve better their satisfaction with health (p = 0.006) and finances (p = 0.011). Respondents aged over 35 years are more satisfied at one-year follow-up with their responsibilities (p = 0.046). Income level does not appear to have a significant influence in the evolution of satisfaction except concerning local services, which is lower at one-year follow-up for everyone, excluding persons with the minimum legal wage level (p = 0.002). The same group shows also better improvement of their satisfaction concerning the opinion of others (p = 0.048) and the wealthiest improve better in terms of satisfaction about their life in general (p = 0.050). Respondents with the lowest level of education show better improvement compared with the others in terms of health satisfaction (p = 0.044). Those who live in semi-private accommodation experience increase better their satisfaction concerning their housing, unlike those living in private homes or who are homeless (p = 0.036). Satisfaction concerning relations with others change over time: the homeless improve whereas those living in sheltered accommodation deteriorate (p = 0.023). Finally, satisfaction regarding relationship with the family deteriorates, especially in the category of the divorced, separated and never-married (p = 0.000), however, satisfaction with health is better for those divorced whilst it remains unchanged for the others (p = 0.032). Global satisfaction with housing slightly increases for everyone except for those married or widowed (p = 0.038).At baseline, no variables are found to influence the global satisfaction in a multiple regression analysis using the variables that show significant influences: centre and income level. However, when a multiple regression is conducted on the variables which have an influence on a one-year evolution of global satisfaction namely: centre, gender, income and marital status, the latter remains significant and all other influences disappear.Concerning the global satisfaction score, patients differ across centres regarding 3 types of symptoms: slowness/under-activity, neurotic symptoms and alcohol problems  and it is at a level that is only just significant.Most of the differences concerning the various sociodemographic variables appeared at one-year follow-up when some patients had left and one of the centres was missing. Consequently, the differences should be interpreted with caution since the drop-out rate could be due to many reasons linked to the health status of the person. However, it is worth noting that we found no difference in baseline satisfaction between respondents and non-respondents at one-year follow-up, except in Lyon (p = 0.008) where non-respondents at one-year follow-up were associated with greater satisfaction at inclusion.In addition, it should be noted that all patients included had to be at least once in contact with a specialised mental health care system during the year of inclusion. This excludes those who were in remission as well as those who did not have access to specialised care and unfortunately, we are not able to check any differences. Table As with the majority of QOL research in both general and mentally ill populations -34, we dWe did not find many differences between young and old patients, but we did find one concerning finances, which was in favour of the older respondents as in the case with most QOL studies done among the general population and the mentally ill, which found that the older the population the more satisfied they are with their QOL, particularly in the area of finances ,34,37.Living conditions, such as living arrangements, have been found to impact on the subjective QOL of individuals with severe mental illness. In all studies, the least restrictive living arrangements were associated with better QOL ,38,39. IA study by Fabian  showed tMost of the epidemiological research to date has systematically found increased well-being and mental health in people with higher levels of education ,41. HoweGlobal comparisons by centres may also reflect the global resources provided to those suffering from severe mental health disorders. In a similar attempt to compare diverse centres in diverse countries, Gaite et al  state thFinally, according to the evolution over a one-year period, marital status appears to be one of the most important variables in terms of satisfaction in many areas, as shown in the work of Salokangas and colleagues , which fThis study replicates many previous findings, however, its originality stems from the variety of EU countries where the patients were treated: these countries have quite different resources, medical as well as social, and the living conditions of patients are very different. However, the main differences as far as their QOL is concerned depend very much on extra-psychiatric variables, principally marital status and income and not so much on clinical variables.Concerns of patients are very similar to those of the non patient populations and income is a serious concern: finances and relationships with others, including love life, are the areas where they are the most dissatisfied.QOL integrates many dimensions and this work shows that an improvement in an area may raise problems in another: for example, being in sheltered housing increases satisfaction with housing but at the same time seems to deteriorate the relationship with others while making no difference in remaining areas.Globally, with largely different resources, after one year spent under the diverse psychiatric care systems, the patients' satisfaction with finances increases, which may indicate some efficiency on the part of psychiatric teams in gathering subsidies for them. However, satisfying relationships with others including love life are a far more difficult goal to reach for such patients with chronic schizophrenia who experience considerable handicaps in those areas essential for their own conception of QOL.QOL Quality of LifeICD International Classification of DiseasesSCAN Schedules for Clinical Assessment in NeuropsychiatrySLDS Satisfaction with Life Domains ScalePHSD Past History and Sociodemographic Description scheduleNFCAS Needs For Care Assessment ScheduleThe author(s) declare that they have no competing interests.VKM was involved in the design of the study, statistical analysis and drafting of the manuscript. MX, BMK, JD, EL, JP, JLR and DW participated in the design of the study and data collection, and provided comment on the content of the manuscript. AS and CSD were involved in the revision of the manuscript.The pre-publication history for this paper can be accessed here:


It is common in asthma and allergy clinics to see patients presenting with upper and lower airway symptoms that are induced by chemicals and scents and not explained by allergic or asthmatic reactions. Previous studies have shown that these patients often have increased cough sensitivity to inhaled capsaicin; such sensitivity is known to reflect the airway sensory reactivity. The aim of this study was to evaluate the duration of symptoms induced by chemicals and scents and to measure health-related quality of life (HRQL) in patients with chemically induced airway symptoms. We also wished to determine and compare repeatability of the cough response to capsaicin inhalation, and to evaluate the patients’ airway sensory reactivity in a long-term perspective.Seventeen patients with a history of at least 12 months of airway symptoms induced by chemicals and scents were followed over 5 years with repeated questionnaires, measurements of HRQL, and capsaicin inhalation tests.The symptoms persisted and did not change significantly over time, and the patients had a reduced HRQL that did not change during the 5-year period. The capsaicin sensitivity was increased at the start of the study, the cough sensitivity was long-lasting, and the repeatability of the capsaicin inhalation test was considered to be good in a long-term perspective.Upper and lower airway symptoms induced by chemicals and scents represent an entity of chronic diseases, different from asthma or chronic obstructive pulmonary disease, with persistent symptoms, a reduced HRQL, and unchanged sensory hyperreactivity. Common symptoms are heavy breathing, difficulty getting air, cough, hoarseness, phlegm, nasal blockage, rhinorrhea, and eye irritation. The symptoms are often misinterpreted as asthma and/or allergy. Sensory hyperreactivity (SHR) is one suggested explanation for these airway symptoms induced by chemicals and scents , but the diagnosis of SHR implies that just one organ is affected—the airways—whereas in MCS, symptoms from multiple organs are involved. However, some patients with SHR also complain of more general symptoms, such as sweating, dizziness, headache, and fatigue, bordering on a diagnosis of MCS . MCS is Capsaicin, which stimulates the unmyelinated C-fibers of the sensory nervous system, has long been used to assess cough sensitivity related to airway sensory nerves . InhalatHealth-related quality of life (HRQL) is a measure of how diseases and symptoms affect health, well being, and the ability to function in daily life. The Nottingham Health Profile (NHP) questionnaire was developed at Nottingham University (UK) for measuring subjective health status and has been used in several studies of various chronic illnesses and conditions . Bilingua) evaluate the duration of symptoms and to measure HRQL in patients with airway symptoms induced by chemicals and scents; b) determine and compare repeatability of the cough response to capsaicin inhalation; and c) evaluate the patients’ sensory reactivity in a long-term perspective.The aims of the present study were to The study group included 17 patients  who were consecutively selected over a period of about 9 months, when they were referred to our outpatient asthma and allergy clinic because of symptoms suggestive of asthma or allergies accompanied by treatment failure. They were screened using a questionnaire on airway symptoms and symptoms in response to chemicals and scents. The patients had at least a 1 year (median 9 years) history of upper and lower airway symptoms induced by chemicals and scents. Within the last 3 years, all patients had had a skin prick test (SPT) with a standard panel of 10 allergen sources common to Sweden. The SPT was negative for all of the patients except for two who had a minor positive reaction to mugwort, which was regarded as being without clinical importance. The methacholine test, administered according to the method described by Informed consent was obtained from all patients. The study was approved by the Regional Ethical Review Board of Göteborg, Sweden.The patients were followed over a period of approximately 5 years. The patients saw their ordinary physician during the follow-up time, and we did not interfere in their treatment. During the first year, patients visited the clinic four times for a capsaicin inhalation test. They then visited the clinic approximately once a year during the following 4 years. At each study visit, the patients underwent a capsaicin inhalation test . Before the first appointment, and once per year thereafter, the patients answered a local questionnaire and their HRQL was evaluated . All of the questionnaires were handed out to the patients and answered before the capsaicin inhalation test. If a patient was unable to come to the clinic, the questionnaires were sent by mail, completed at home, and mailed back.At the beginning of the study, the patients answered a local questionnaire about symptoms and triggering factors for symptoms. They were asked to score symptoms that they had experienced over the previous year on a scale of 0–3 . Fourteen symptoms were analyzed: heavy breathing, difficulty getting air, chest weight, cough, phlegm, throat irritation, hoarseness, nasal blockage, rhinorrhea, eye irritation, sweating, headache, dizziness, and fatigue. To allow test–retest evaluation of the symptom score questionnaire, the patients completed this questionnaire twice at the beginning of the study. The patients were also asked about their working capacity and the medication they used at the start of the study and then once each year.HRQL was assessed using the NHP questionnaire, a generic, self-administered instrument for measuring various aspects of HRQL . The queWe used norm and reference values distributed by age and sex for parts I and II of the NHP. These values are based on data from larger populations that are currently used in family practice .We prepared a stock solution of capsaicin . We then diluted the stock solution with 0.9% saline, containing 1% ethanol by volume, to prepare aqueous provocation solutions of 0.4, 2, and 10 μmol/L. The provocation solutions were prepared regularly and stored frozen. A capsaicin aqueous solution of 100 μmol/L retains total stability after 3 months of storage in a freezer .1) was measured using a calibrated spirometer  before and after the inhalation test, and the highest of three values was recorded.Capsaicin was nebulized  and inhaled through a mouthpiece  by tidal volume breathing; a nose clip was not used. Saline (1 mL) and the three increasing concentrations of capsaicin  in a 1-mL solution were inhaled to completion, or for a maximum of 6 min, in order to induce coughing; this was followed by a 4-min rest period. The total number of evoked coughs was counted for 10 min from the onset of each inhaled capsaicin concentration. Cough registration was performed by the same counter using a tape recorder. The total duration of each capsaicin inhalation test was approximately 45 min. On the first three occasions, no limit was set on the number of coughs. In the following tests, however, out of consideration for the patients, provocation was stopped if one dose of capsaicin provoked >70 coughs. The forced expiratory volume in 1 sec  value < 0.05 was considered statistically significant.A probability , moving to another city (subject 7), fear of experiencing prolonged airway symptoms due to the provocation (subject 12), and pregnancy or expected pregnancy (subjects 11 and 17).1 was 96% of that predicted before the first capsaicin inhalation test, and no significant difference was found after the capsaicin provocations. During the 5-year follow-up, we found no significant changes in the median values of FEV1 compared with the initial baseline values.The median value of FEVrs = 0.77; p < 0.01) indicating good reliability for the questionnaire.The test–retest reliability of the symptom score questionnaire was high (p < 0.01) score for social isolation than the reference group. There were no statistically significant differences compared with the reference group in the other five dimensions . Part II of the NHP is presented in p < 0.05), housework (p < 0.05), social life (p < 0.01), hobbies (p < 0.01), and holidays (p < 0.05). Over the 4-year period the patients demonstrated no significant changes in any parts of the NHP compared with their initial evaluation.In the primary evaluation for part I of the NHP, patients had a significantly higher (p < 0.05).We counted the number of coughs by listening to the tape recordings. The patients coughed dose-dependently during the capsaicin provocations . Of the r = 0.78; p < 0.001)  . The SD < 0.001) .n = 15) of the same participants attended: the last provocation of the first year and the provocation of the third year. The number of coughs after inhalation of 2 μmol/L capsaicin correlated significantly between these two provocation occasions   . The SD < 0.001) .In this 5-year study, we followed 17 patients with previously medically unexplained airway symptoms induced by chemicals and scents. These symptoms are often misdiagnosed as asthma or allergy, but they can be recognized using a capsaicin inhalation cough test . AccordiNone of the patients in the present study demonstrated any serious adverse reaction or bronchoconstriction after the capsaicin inhalation test. In a recent review, Capsaicin-induced cough can, to a certain extent, be voluntarily suppressed or enhanced . Some inMedically unexplained physical symptoms are common in clinical care and within the general population; examples include chronic fatigue syndrome, fibromyalgia, MCS, idiopathic environmental intolerances, somatoform disorders, and “Gulf War syndrome.” These symptoms are associated with extensive morbidity and have a significant impact on everyday functions . The assIn conclusion, airway symptoms induced by chemicals and scents can be regarded as a chronic condition and may represent an entity of chronic diseases, with persistent symptoms, a reduced HRQL, and unchanged long-lasting sensory hyperreactivity. The repeatability for the capsaicin inhalation test is good in a short-term and long-term perspective. Although the capsaicin inhalation test was valuable for diagnosing these patients, the cause of their symptoms remains obscure, and there is currently no effective treatment; this emphasizes the need for future pathophysiologic research.


The objective of the study was, with multidetector computed tomography (CT) as the reference method, to determine whether bone erosions in rheumatoid arthritis (RA) metacarpophalangeal (MCP) joints detected with magnetic resonance imaging (MRI) and ultrasonography (US), but not with radiography, represent true erosive changes. We included 17 RA patients with at least one, previously detected, radiographically invisible MCP joint MRI erosion, and four healthy control individuals. They all underwent CT, MRI, US and radiography of the 2nd to 5th MCP joints of one hand on the same day. Each imaging modality was evaluated for the presence of bone erosions in each MCP joint quadrant. In total, 336 quadrants were examined. The sensitivity, specificity and accuracy, respectively, for detecting bone erosions (with CT as the reference method) were 19%, 100% and 81% for radiography; 68%, 96% and 89% for MRI; and 42%, 91% and 80% for US. When the 16 quadrants with radiographic erosions were excluded from the analysis, similar values for MRI  and US  were obtained. CT and MRI detected at least one erosion in all patients but none in control individuals. US detected at least one erosion in 15 patients, however, erosion-like changes were seen on US in all control individuals. Nine patients had no erosions on radiography. In conclusion, with CT as the reference method, MRI and US exhibited high specificities  in detecting bone erosions in RA MCP joints, even in the radiographically non-erosive joints (96% and 92%). The moderate sensitivities indicate that even more erosions than are seen on MRI and, particularly, US are present. Radiography exhibited high specificity (100%) but low sensitivity (19%). The present study strongly indicates that bone erosions, detected with MRI and US in RA patients, represent a loss of calcified tissue with cortical destruction, and therefore can be considered true bone erosions. Radiography is the mainstay of the evaluation of structural joint damage in patients with rheumatoid arthritis (RA). It is a routine procedure for diagnosis and prognostication in RA patients, and is an important end-point in clinical trials ,2. DetecMagnetic resonance imaging (MRI) has been demonstrated to be more sensitive than radiography in detecting erosive changes in RA, especially the subtle changes that occur in early disease -11,13,14Ultrasonography (US), although less validated, has been reported to be more sensitive than radiography and comparable to MRI in detecting bone erosions in RA metacarpophalangeal (MCP) ,20 and mConventional radiography is based on attenuation of X-rays, and calcified tissues such as bone are readily depicted because of their markedly greater attenuation in comparison with the surrounding soft tissues. Because imaging with MRI and US does not depend on X-rays, it has been speculated to which extent erosions detected using these modalities reflects true loss of calcified tissue, that is, are true erosions,27.Computed tomography (CT) is a tomographic radiographic imaging method that visualizes calcified tissue with high resolution, and CT can be considered a standard reference for detecting destructions of calcified tissue, such as bone erosions in RA ,26. By uNo comparative studies of CT, MRI, US and radiography in evaluating erosive bone changes in RA MCP joints have been reported. Although one study compared CT and MRI with respect to their ability to evaluate bone erosions in RA wrists , data frSeventeen patients with RA fulfilling American College of Rheumatology 1987 criteria  and fourPatients were recruited from the Department of Rheumatology, Copenhagen University Hospital at Hvidovre. All patients were selected from former MRI studies, and were eligible to participate in the study if they, in at least one of the examined MCP joints, at a previous examination had at least one radiographically invisible MRI lesion, presumed to be an erosion. All imaging procedures were performed at the Department of Radiology, Copenhagen University Hospital at Herlev.The study was approved by the local ethics committee, and written informed consent was obtained from all participants.A Philips Mx8000 IDT multidetector unit  was used for all examinations . Patients were placed in the prone position with the arm stretched and the palm facing down. Images with a voxel size of 0.4 × 0.4 × 1.0 mm were obtained, and software for multiplanar reconstruction created axial and coronal reconstructions with a slice thickness of 1.0 mm , and these were used for image evaluation Figures . In ordeA Philips Panorama 0.6 T unit , using a receive-only three channel phased solenoid coil, was used for all examinations. Patients were placed in the supine position, with the hand alongside the body and the palm facing the body. Acquired images included a coronal T1-weighted three-dimensional fast field echo . Multiplanar reconstructions of the T1-weighted three-dimensional fast field echo sequence were done in the axial and coronal planes with a slice thickness of 0.4 mm, and these were used for image evaluation  with experience in US of RA joints from previous studies. The same Philips 5000 HDI unit  with a 15-7 MHz linear array hockey stick transducer was used for all examinations. The dorsal and palmar aspects of the 2nd to 5th MCP joints, the radial aspect of the 2nd MCP joint and the ulnar aspect of the 5th MCP joint were examined with longitudinal and transversal scans  with a resolution of 0.3 mm. Posterior anterior and Nørgaard  projectiAll imaging modalities were evaluated with investigators blinded to clinical and other imaging data. Each MCP joint quadrant  was scored for the presence or absence of erosions. The localizations of erosions were marked on a preformed scoring sheet, which allowed exact positioning of erosions in all three planes. Erosions on CT were defined as a sharply demarcated area of focal bone loss seen in two planes, with a cortical break (loss of cortex) seen in at least one plane. Definitions of MRI erosions were as suggested by Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis MRI Scoring System (RAMRIS)  . In this analysis MRI exhibited a sensitivity, specificity and accuracy of 65%, 96% and 90%, respectively. For ultrasonography the corresponding figures were 30%, 92% and 80% .The concordance between readings by the two CT readers  was 90%.The main purpose of the present study was to investigate whether erosions detected by MRI and US could be confirmed by CT . With CT as the standard reference method, high specificity of MRI and US in detecting bone erosions in RA MCP joints was demonstrated, even when only radiographically normal MCP joints  were considered. This study strongly indicates that radiographically invisible bone erosions detected by MRI and US are true erosive changes.All patients were selected from former MRI studies and were eligible to participate in the study if they had at least one radiographically invisible MRI lesion, presumed to be an erosion. This selection was made in order to include only patients whose joints were not too severely damaged, that is, the patients in which MRI and US would be expected to have the greatest clinical value. Clearly, the sensitivity of radiography, MRI and US would have been higher if joints with extensive erosive changes had been included.Previous studies -11,14 haSignal on radiography and CT is based on attenuation of X-rays, and bone and other calcified tissues are easily depicted because of markedly higher X-ray attenuation by these tissues than by the surrounding soft tissues. The signal on magnetic resonance images is not dependent on X-rays but on presence of mobile protons in the tissue, and as the water content in bone is very low cortical bone is depicted as signal voids silhouetted against signal-emitting bone marrow and periosseous tissues. It has been argued that MRI is not well suited to visualizing lesions of calcified tissue, and the nature of bone erosions visualized with MRI, that are not visible on radiography, has been questioned . In thisTo our knowledge, no published studies have compared CT, MRI, US and radiography in small RA joints. In a recent study conducted by Perry and coworkers , a compaOverall, the sensitivity of US in detecting bone erosions in the present study was lower than the sensitivity of MRI. Several other studies have reported that the sensitivity of US is best at the most easily accessible joints , where visualization of the joint is possible from three aspects ,22. In tIn two patients no erosions were detected on US, however, in all four healthy control individuals 'false positive' erosions were registered, whereas none of these were seen on CT, MRI and radiography. On US three control individuals had one erosion-like lesion each, whereas in the last control individual eight sites were registered with erosion-like lesions. It should be noted that the latter control individual developed a HLA-B27 positive arthritis one year later, which was treated with sulfasalazine. There was no tendency toward any specific regions in which erosion-like changes were seen on US. That erosion-like changes were observed in healthy control individuals in the present study is in agreement with previous US studies ,21, evenWhen finding pathological changes in healthy control individuals, using any diagnostic procedure, it should be considered whether the method is too sensitive, and our findings question whether the definition of US erosions used in the study is optimal. However, there is an inherent, usually divergent balance between the sensitivity and specificity of a test. In clinical trials, in which the diagnosis is established, a high sensitivity is often of fundamental importance. However, in a diagnostic setting high specificity may have the highest priority, because the diagnosis has important implications for classification and treatment.Despite descriptions in the literature of CT findings in RA peripheral joints ,26,34, CExamination of the inter-reader agreement was not the objective of this study, and because previous papers have reported good inter-reader agreements for the readers of MRI (BE)  and US  are needed before any general recommendations on the use of CT in RA can be given.MRI and US exhibited high specificities in detecting bone erosions in RA MCP joints, even in radiographically non-eroded joints, when CT was used as the reference method. The moderate sensitivities of MRI and US indicate that even more erosions than were detected using MRI and US were present. Radiography had markedly lower sensitivity for bone erosions than CT, MRI and US.The present study strongly indicates that bone erosions, detected by MRI and US in RA patients, represent loss of calcified tissue with cortical destruction, and therefore can be considered true bone erosions.CT = computed tomography; MCP = metacarpophalangeal; MRI = magnetic resonance imaging; OMERACT = Outcome Measures in Rheumatology; RA = rheumatoid arthritis; RAMRIS = Rheumatoid Arthritis MRI Scoring System; US = ultrasonography.UMD participated in the study development and recruitment of patients, conducted data evaluation and statistical analysis, and prepared the manuscript draft. BE participated in the study development, performed the evaluation of magnetic resonance images, and was involved in patient recruitment. MC-P performed the ultrasonographic examinations. MH was involved in the CT scanning protocol and evaluated CT images. EN performed the evaluation of radiographs. MS participated in study development. JM was involved in the MRI scanning protocol and performed all MRI examinations. HT participated in study development and gave substantial input to the data evaluation and manuscript preparation. MØ participated in the study development, was involved in the CT and MRI scanning protocol, evaluated CT images, and gave substantial input to the data evaluation and manuscript preparation. All authors read and approved the final manuscript.


We aimed to evaluate the prevalence, frequency and type of leisure-time physical activity (LTPA) among adults in Greece, as well as its relationship with socio-demographic, lifestyle and clinical characteristics of these people.From May 2001 to December 2002 we randomly enrolled 1514 men and 1528 women, without any evidence of cardiovascular or any other chronic disease. The sampling was stratified by the age – gender distribution of (census 2001) of the greater area of Athens. Weekly energy expenditure assessed by considering frequency, duration (in minutes) and intensity of sports related physical activity during a usual week.53% of men and 48% of women were classified as physically active. Men were more likely to be active as compared to women (p < 0.05), while the lowest activity rates were observed in 40 to 49 years old participants (p < 0.01). Physically active people had higher occupation skills, were more likely to live in rural areas, to be unmarried, non smokers and they were devoted to a healthier dietary pattern, as compared to sedentary, irrespective of age and sex . In addition, the cumulative risk factors score of obesity, hypertension, hypercholesterolemia and diabetes, was inversely associated with activity status (p < 0.001). Finally, physically active men and women were less likely to report depressive symptoms (p < 0.01), after various adjustments were made.Half of the studied population reported physically inactive, indicating that sedentary lifestyle becomes a serious epidemic in Greece. High occupation skills, non-smoking, devotion to a healthier dietary pattern and a better cardiovascular risk factors profile were some of the determinants of physically active people. Several observational and clinical studies suggest that physical activity substantially reduces the risk of dying of coronary heart disease, stroke, and colon cancer -4. It alData regarding the prevalence of physical activity and its association with various characteristics of Greek men and women are lacking. Therefore, the aim of this work is to evaluate the prevalence of leisure-time physical activity (LTPA) and to investigate its association with various socio-demographic, lifestyle and behavioural characteristics of Greek adults.The "ATTICA" study is a health and nutrition survey, carried out in the province of Attica , where Athens, is a major metropolis. The sampling was random, multistage and based on the city – gender – age distribution of the province of Attica (census of 2001). The study's design anticipates enrolling only one participant per household. The main goals of the ATTICA study were to record the distribution of several blood lipids, inflammatory, oxidation, coagulation, thrombotic and clinical factors and to explore the associations between these factors with several socio-demographic, lifestyle and psychological characteristics of the participants.P-value). Also, those living in institutions were excluded from the sampling. The participants had no clinical evidence of cardiovascular or any other atherosclerotic disease, as well as chronic viral infections dental problems or any type of surgery in the past week. They also exhibited no signs of cold, flu, or any acute respiratory infection.From May 2001 to August 2002, 4056 inhabitants from the above area were randomly asked to participate in the study. Of those, 3042 agreed to participate (75% participation rate); 1514 of the participants were men  and 1528 were women . Between 40 – 49 years old there were 48% men and 52% women. The number of the participants was determined by power analysis and chosen to evaluate two-sided differences between the normally distributed investigated parameters and physical activity groups greater than 10%, achieving statistical power > 0.80 at < 0.05 probability level (st tertile), medium physical activity (2nd tertile) and high physical activity (3rd tertile). Therefore, 1st, 2nd and 3rd tertile included 217 men and 205 women, respectively. We have also recorded the type of exercise, i.e. resistance (i.e. any technique that uses progressive resistance to increase muscular strength) or endurance training. The presence of occupational physical activity was recorded , but was not taken into account for the analysis due to difficulties in evaluation and standardization. This exclusion may confound our findings, but the large sample size and the randomised procedure for the selection of the participants can spread the subjects who reported occupational exercise equally in both groups of the study.We used a translated version of a validated questionnaire  of weeklAlthough there are some concerns with self-reported physical activity, the introduced evaluation is now considered reliable, valid and has been used by many other similar studies .In addition to the physical activity status, the study's questionnaire included demographic characteristics like age, gender, family status , financial status , and occupational status as well as education level. The educational level of the participants  was measured in years of school. Occupation was also recorded and evaluated through a ten-point scale from unskilled – hand workers  to executive – skilled workers .Information about smoking habits was collected using a standardized questionnaire developed for the Study. Current smokers were defined as those who smoked at least one cigarette per day. Never smokers those who have never tried a cigarette in their life and former smokers were defined as those who had stopped smoking more than one year previously. In all multivariate statistical analyses cigarette smoking habits were taken into account using the pack-years (cigarette packs per day × years of smoking). However, in order to correct for the amount of nicotine containment in various types of cigarettes smoked , we assigned a weight in each different type of cigarette – pack, using the 0.8 mg/cigarette as the standard.Consumption of non-refined cereals and products, vegetables, legumes, fruits, olive oil, dairy products, fish, pulses, nuts, potatoes, eggs, sweets, poultry, red meat and meat products were measured as an average per week during the past year through a validated food – frequency questionnaire (FFQ), from the Department of Nutritional Epidemiology of Athens Medical School . The freDepressive symptomatology was assessed using a translated and validated version of the Zung Self-Rating Depression Scale (ZDRS) . The ZDRELKA using aneroid manometric sphygmometer, Von Schlieben Co, West Germany). Patients whose average blood pressure levels were greater or equal to 140/90 mm Hg or taking antihypertensive medication were classified as hypertensives. Body mass index was calculated as weight (in kilograms) divided by standing height (in meters squared). Obesity was defined as body mass index > 29.9 kg/m2. Also, the investigators of the study recorded a detailed medical history of the participants.The blood samples were collected from the antecubital vein between 8 to 10 a.m., in a sitting position after 12 hours of fasting and avoiding of alcohol. The biochemical evaluation was carried out in the same laboratory that followed the criteria of the World Health Organization Lipid Reference Laboratories. Serum cholesterol was measured using chromatographic enzymic method in a Technicon automatic analyzer RA-1000. The intra and inter-assay coefficients of variation of cholesterol levels did not exceed 5%. Participants with total serum cholesterol levels greater than 200 mg/dl or those taking lipid-lowering agents were classified as hypercholesterolemic and those with blood sugar > 125 mg/dl or the use of antidiabetic medication were classified as diabetic. Arterial blood pressure was measured at end of the physical examination with subject in sitting position for 25–30 minutes. Three measurements were abtained from the right arm (Details about the aims and methods of the ATTICA study have been presented elsewhere .r or Spermans's rho (for skewed variables) correlation coefficients. Comparisons between normally distributed continuous variables and categorical were performed by the use of Analysis of co-Variance (multi- way ANCOVA), after controlling for homoscedacity, and potential confounders. Kolmogorov-Smirnov criterion was used for the assessment of normality. In the case of asymmetric continuous variables the tested hypotheses were based on the calculation of the Kruskal – Wallis test. Associations between the investigated variables and physical activity levels were tested through fixed effects models, after the adjustment for several potential confounders and its interactions with physical activity status. The assumptions of linearity and homoscedacity were graphically tested by plotting fitted values against standardised residuals. Multiple logistic regression analysis estimated the odds ratio of being at a specific health condition with respect to physical activity status. Deviance residuals evaluated models' goodness of fit. All reported P-values are based on two-sided tests and compared to a significance level of 5%. However, due to multiple significance comparisons we used the Bonferronni correction in order to account for the increase in Type I error. SPSS 11.0.5 software  was used for all the statistical calculations.Continuous variables are presented as mean values ± standard deviation, while categorical variables are presented as absolute and relative frequencies. Associations between categorical variables were tested by the use of contingency tables and the calculation of chi-squared test. Correlations  between continuous or discrete variables were tested by the calculation of Pearson's r = -0.23, p = 0.02, r = -0.34, p = 0.001, and r = -0.21, p = 0.0001, respectively).Eight hundred and two (53%) of men and 733 (48%) of women were classified as physically active. Table Furthermore, from physically active participants, 5% of men and 2% of women reported only resistance training, while 7% of men and 12% of women reported only endurance training. Thirty five percent of men and 25% of women reported that they were engaged in organised sports . When we compared participants in organised sports with non-participants, those who participated in organised sports were more often persistent exercisers as compared to those who did not .Table Table An inverse relationship was observed between physical activity status and ZDRS, which indicates that men and women who used to exercise were less likely to have depressive symptoms as compared to sedentary , irrespective from the effect of various potential confounding factors like age, sex, educational, financial and occupational status. Moreover, participants in the highest tertile of physical activity had 41% lower odds  of having major depressive syndromes (i.e. ZDRS > 60), after controlling for the previous potential confounding factors.r = -0.46, p < 0.001), after adjusting for age and sex. Participants in the highest tertile of physical activity had 48% lower odds of being obese , after adjusting for age, sex, smoking habits, blood pressure, total cholesterol and glucose levels. The prevalence of hypertension was 38% in men and 24% in women. Physical activity was also associated with lower odds of being hypertensive , irrespective of age, sex, smoking habits, total cholesterol and glucose levels. Moreover, compared to sedentary, people in the highest tertile of physical activity had on average 15 mm Hg lower systolic (p = 0.02) and 8 mmHg lower diastolic (p = 0.04) blood pressure levels, after adjusting for age, sex, body mass index and diet score. We have also observed that 54% of men and 60% of women had total serum cholesterol levels <200 mg/dl. No association was observed between physical activity and presence of hypercholesterolemia (p = 0.76).An inverse relationship was observed between body mass index and physical activity score , after adjusting for age, sex and smoking habits. Figure Afterwards we calculated the cumulative distribution of four major cardiovascular risk factors, i.e. obesity, hypertension, hypercholesterolemia, and diabetes. We observed an inverse relationship between physical activity index and the cumulative score of risk factors . A description of the profile of the participants showed that physically active people had higher occupation skills, were more likely to live in rural areas, to be unmarried, to be non smokers and they were devoted to a healthier dietary pattern, as compared to sedentary, irrespective of age and sex. In addition, the cumulative score of four major cardiovascular risk factors, i.e. obesity, hypertension, hypercholesterolemia, and diabetes, was inversely associated with the applied physical activity index. Finally, physically active men and women were less likely to report depressive symptoms.Physical activity has been related with social status in some, but not all studies. For example, in a population-based sample from Copenhagen , the invWe also found that participants who were devoted in organised sports and members in sports clubs were more frequently persistent exercisers as compared to those who did not. This is in accord to the reports from several other investigators, which observed that participation in organised sports was associated with the stability of physical activity -17. ThusWe observed that men were more likely to be physically active as compared to women, irrespective of age. These gender differences are pronounced in most countries. For example, it has been reported that the proportions of girls exercising actively is approximately half of that of boys among 15-year-olds in Greenland, Lithuania and Greece . The issRegarding marital status we observed that never married participants were more likely to be physically active as compared to married or divorced/widowed, independent from age and sex of the participants. There are very sparse data in the literature concerning the relationship between marital status and physical activity. In a population-based study of men and women from the US , the invDepression constitutes a worldwide health problem, because is associated with functional impairment in normal life and at work, poor compliance with medical therapy and lifestyle risk factors interventions . Much diFurthermore, we confirmed previous reports concerning an inverse association of physical activity with the prevalence of obesity and hypertension -36, whilThis is a cross-sectional study that cannot provide causal relationships, but only state hypotheses for future research. Occupational physical activity which was not taken into account in the present study, and misreporting of physical activity status due to self-reports may confound, at least in part, the strength of the observed relationships. Another limitation is that LTPA has been related to a healthier lifestyle habits and consequently to a better health status. For example, adoption of a healthier dietary pattern or reduced smoking habits may be more common among individuals who were devoted to leisure time exercise. Thus, the benefits from LTPA on the prevalence of risk factors Figure  cannot pA considerable proportion of the population studied reported physically inactive, indicating that sedentary lifestyle becomes a serious epidemic in Greece, and especially in women. We have also illustrated the socio-demographic profile of people that are physically active and we revealed the relationships between physical activity and various lifestyle behaviors, the presence of depressive symptoms and several metabolic disorders associated with cardiovascular risk. Despite the limitations of the cross-sectional design of the present study, our findings may carry an important public health message, i.e. to inform the community and especially middle-aged, low socio-economic status people living in urban areas, about the benefits derived from physical activity in order to prevent future cardiovascular events and other psychological disorders.The author(s) declare that they have no competing interestsCP = drafted the paper, was the principal investigator, and had the concept, and design of the study, DBP = wrote the paper, was the principal investigator, and had the concept and design of the study, performed the data analysis, YL = drafted the paper, participated in the clinical evaluation of the participants and CS = drafted the paper.The pre-publication history for this paper can be accessed here:


Caulimoviridae in the genus Badnavirus. RTBV has a long open reading frame that encodes a large polyprotein (P3). Pararetroviruses show similarities with retroviruses in molecular organization and replication. P3 contains a putative movement protein (MP), the capsid protein (CP), the aspartate protease (PR) and the reverse transcriptase (RT) with a ribonuclease H activity. PR is a member of the cluster of retroviral proteases and serves to proteolytically process P3. Previous work established the N- and C-terminal amino acid sequences of CP and RT, processing of RT by PR, and estimated the molecular mass of PR by western blot assays.Rice tungro bacilliform virus (RTBV) is a pararetrovirus, and a member of the family E. coli of putative domain was affected by the presence or absence of the active site in the construct. Analysis of processing of CP by PR, using pulse chase labelling experiments, demonstrated that the 37 kDa capsid protein was dependent on the presence of the protease in the constructs.A molecular mass of a protein that was associated with virions was determined by in-line HPLC electrospray ionization mass spectral analysis. Comparison with retroviral proteases amino acid sequences allowed the characterization of a putative protease domain in this protein. Structural modelling revealed strong resemblance with retroviral proteases, with overall folds surrounding the active site being well conserved. Expression in in vitro expression studies are evidence to consider the putative domain as being the protease domain. Analysis of expression of different peptides corresponding to various domains of P3 suggests a processing of CP by PR. This work clarifies the organization of the RTBV polyprotein, and its processing by the RTBV protease.The findings suggest the characterization of the RTBV protease domain. Sequence analysis, structural modelling,  Caulimoviridae which comprises 6 genera [Plant pararetroviruses are classified as members of the family 6 genera . Like re6 genera ,3. Howev6 genera .Retroviruses and pararetroviruses show similarities in their molecular organization and replication process and are phylogenetically related. These groups of viruses direct the production of a terminally redundant RNA which is used as a replicative intermediate and as mRNA. Many of the genes encoded by pararetroviruses are homologous in sequence and/or analogous in function to those of retroviruses. The genome of all replication-competent retroviruses consists of three major genetic elements that are arranged in the order gag-pol-env . Each protein is produced as a result of frameshifting during translation, or suppression of stop codons in the polyproteins. Products of the gag ORF represent the structural components of the viral matrix, i.e. capsid and nucleocapsidproteins; the pol domains generally comprise the protease, reverse transcriptase, ribonuclease and an endonuclease/integrase. Pararetroviruses encode the gag-pol core, but lack an integrase, as viral DNA integration into the host chromosome is not required .Retrovirus and pararetrovirus polyproteins are believed to be processed by their own aspartate proteases ,6,7. TheBadnavirus in the family Caulimoviridae [Waikivirus in the family Sequiviridae [Nephotettix virescens [Rice tungro is a major rice disease in southeast asia and is caused by a double infection by two viruses ,9: Rice oviridae , and Riciviridae ,13. RTBViviridae  and RTSVirescens ,15.in vivo revealed a major protein of 13.5 kDa in virus preparations, by using an antibody raised against the domain aa 881–1098 [RTBV genome is a double stranded DNA of 8.0 kbp with two site-specific discontinuities resulting from replication by reverse transcriptase ,16. The 881–1098 . The ant881–1098 .in silico modelling and in vitro expression studies. Analysis of products of in vitro processing of P3 suggests that RTBV aspartate protease is involved in the release of the CP from the polyprotein P3.In this paper, we used mass spectrometry analysis to characterize the RTBV protease domain in a protein associated with purified virions, and confirm the hypothesis by In-line HPLC electrospray ionization was used to determine the molecular mass of proteins that were isolated in preparations of RTBV. Several peaks were observed using this method, none of which correspond to the known molecular mass of the CP subunits . Many ofBy comparing the known sequence of P3 protein in RTBV with aspartate proteases encoded by other retroviruses we predicted that five possible proteins could be derived with a molecular mass of 13,794 ± 4 Da that could contain the putative active site domain DSGS (at aa 987–990) and the IIG sequence. The IIG sequence motif is conserved amongst retroviral proteases and is located at aa 1063–1065 in P3. The five predicted proteins Figure  were covThe overall sequence similarity between aspartate proteases is quite low (below 25%) based on pairwise scoring criteria; therefore we applied fold recognition methods to detect remote homologues. The sequence alignment for the proteins selected for analysis showed strong conservation in the active site of the proteins Figure . The paiE. coli and, following induction of gene expression the extracts were subjected to SDS-PAGE, and gels were stained with coomassie blue  were designed to amplify the putative protease domain deduced from the mass spectrometry analysis Figure . DNA usee Figure . The expe Figure .E. coli. After 1 hour induction cultures were labelled with 35S-methionine for five min after which protein extracts were subjected to SDS-PAGE, followed by autoradiography. Multiple bands were observed in cultures that contain each plasmid  mass spectrometry analysis . A singlFive peptide domains, with the predicted mass of the protein identified in virions, were found to contain the active site DSGS, the active site of an aspartate protease, and the conserved region IIG Figure . We compTo confirm if the target sequence is or is not a protease, we used a combination of sequence and structural predictions procedures to build a structural model for the RTBV protease Figure  with RSVE. coli: however, PR did not accumulate in E.coli while mPR was expressed normally and reacted with Ab-RTBV and with Ab-PR antibodies. In other studies, the mutation of D to A in the active site of the RTBV protease was shown to affect its activity [E. coli because the peptide was an active protease that was not tolerated in the host. Previous attempts to express proteases in E. coli have had similar outcomes [Plasmids that encode peptides PR and mPR were introduced for expression in activity . We suggoutcomes ,28.et al., [An antiserum against the region aa 881–1098 of the P3 was produced in previous studies ; this peet al., , which iet al., . With thet al., ,19. Howeet al., ,30. Othein vitro processing of CP by PR was demonstrated in E.coli. If immunoprecipitations with antibodies were not achieved for technical reasons, presence of the 37 kDa peptide was associated with co-existence of CP and active PR in the construct. It is the first time that such a processing is demonstrated for pararetroviruses , where CP and PR are components of the same polyprotein.A previous work conducted in insect cells using baculovirus based constructs, including constructs in which the active site of the protease was mutated revealed that RT was processed by PR . In the Our results clarify the organization of P3, and its processing by its own protease and lead to a more complete understanding of the replication process and possible points of control of pararetroviruses.The RTBV strain used for the analysis was from the International Rice Research Institute . Sequence of the genome was published , with acDSGS  was changed to alanine, resulting in the sequence ASGS. Plasmid pBS-mp/RT was used for further sub-cloning.Plasmid pBS-mp/RT  contain In-line HPLC electrospray ionization mass spectrometry  was empl[[[The RTBV sequence was used as a query for the BLAST program against non redundant databases and PDB databases. No significant hits were identified with suitable e-values by these queries. The sequence was then submitted to fold recognition methods at the metaserver . Reliabl and furt. Models [ and What[[ tools. T[[.The full-length RTBV clone pBSR63A  was usedE.coli DH5-α. The resulting plasmids were designated pTr-PR, pTr-mPR and resulted in synthesis of peptides, named PR, mPR, corresponding to regions between residues 965–1085 . The resulting plasmids were designated pET-MP, pET-MP/PR, pET-P3, pET-MP/mPR, pET-mP3. These plasmids encode (in order) peptides, named MP, MP-PR, P3, MP-mPR, mP3 corresponding to regions between residues 1–606, 1–1195, 1–1675, 1–1195, 1–1675, respectively  declare that they have no competing interests.in vitro expression analysis and pulse chase labelling experiments; ARM performed the structural modelling analysis; AdK analyzed various sequences by computer; RNB and CMF were principal investigators. All authors read and approved the final manuscript.PM carried out the designing of primers, the construction of various plasmids, the


Alzheimer's disease and type 2 diabetes mellitus tend to occur together. We sought to identify protein(s) common to both conditions that could suggest a possible unifying pathogenic role. Using human neuronal butyrylcholinesterase (AAH08396.1) as the reference protein we used BLAST Tool for protein to protein comparison in humans. We found three groups of sequences among a series of 12, with an E-value between 0–12, common to both Alzheimer's disease and diabetes: butyrylcholinesterase precursor K allele (NP_000046.1), acetylcholinesterase isoform E4-E6 precursor (NP_000656.1), and apoptosis-related acetylcholinesterase (1B41|A). Butyrylcholinesterase and acetylcholinesterase related proteins were found common to both Alzheimer's disease and diabetes; they may play an etiological role via influencing insulin resistance and lipid metabolism. Alzheimer's disease and type 2 diabetes mellitus occur with increasing frequency as age advances. Besides, the development of one increases the risk of the other . EpidemiThe enzyme butyrylcholinesterase (EC 3.1.1.1.8) does not have a well-defined physiological function, although it may modulate the phenotypic expression of dyslipidemia and insulin resistance. It is affected by dietary factors, obesity, and dyslipidemia ,7,8While acetylcholinesterase in the brain is chiefly localized to neurons, butyrylcholinesterase is primarily associated with glial cells and endothelial cells .Butyrylcholinesterase was studied in relation to both type 2 diabetes mellitus and Alzheimer's disease in different ethnic groups -13.Despite originating from the endoderm, the pancreas is highly innervated and shares molecular similarities with brain at the level of transcriptome and proteome . LocalizConsidering that butyrylcholinesterase was associated with both type 2 diabetes mellitus and with Alzheimer's disease, and that leads existed for the a role of butyrylcholinesterase in their pathogeneses, we chose it as the reference protein. In addition, genetic variants of the enzyme exist, which may play a role in biological fitness of individuals . Identif-5 of an alignment means that that alignment is highly unique, and not due to error, whereas an E ≥ e-6 means that the alignment might be strong, but more research is needed to verify. The lower the E value, the more significant the score.Data was retrieved from National Centre for Biotechnology Information (NCBI). We took the amino acid sequence of human neuronal butyrylcholinesterase AAH08396.1) as the reference protein and copied it to Word programme in FASTA format. We used BLAST tool in NCBI, and performed protein to protein comparison in humans from the available databases. Taking E-value between 0–12, we obtained 12 sequences that were common to both Alzheimer's disease and diabetes mellitus , acetylcholinesterase isoform E4-E6 precursor (NP_000656.1), and apoptosis-related acetylcholinesterase (1B41|A).Dementia and diabetes increase with age. This is related to the occurrence of atherosclerosis, advanced glycation end product, oxidative stress and the deposit of amyloid. ,5. NeuroThe variable association of BchE and variants with Alzheimer's disease ,23-25 waStudies have linked BchE with the pathogenesis of Alzheimer's disease and diabetes mellitus. BchE may modify the risk of Alzheimer's disease either alone, or in synergy with apoE-epsilon 4 . Its actBchE may be involved in the pathogenesis of type 2 diabetes either by way of amyloid fibrils or by modifying other risk factors of insulin resistance. Amyloid fibrils in pancreatic islets produce excessive superoxide radicals, lipid peroxidation and nitric oxide inactivation, contributing to apoptosis of beta cells . K variaIn addition, increased BchE may predispose aging cells to oxidative stress .Conventional association studies with evaluation of limited phenotypes are laborious, and do not always give unambiguous answers proportionate to the effort incurred . With thComparative genomic study across species provides a more broad-based picture of proteins in terms of evolution; earlier we showed that butyrylcholinesterase (EC 3.1.1.1.8) and its variants were spread in mammals consistent with their evolutionary space, and that homologous sequences were expressed in other life forms, including plants and bacteria ,28.Butyrylcholinesterase  is an alternatively-spliced variant expressed in blood cells, associated with apoptosis. It could be a potential marker and a regulator of apoptosis, being expressed in apoptotic cells. Similarly it could be modulate pro-inflammatory cytokines in macrophages in the periphery, and be differentially expressed by stress in the periphery and in the central nervous system [s system .Insulin signaling abnormalities could be the underlying mechanism affecting the outcome of Alzheimer's disease; insulin resistance and disordered degradation of amyloid seem to link diabetes mellitus with Alzheimer's disease . InsulinAntidiabetic drugs could be potentially useful in treating Alzheimer's disease: PPAR gamma agonists, by improving insulin sensitivity, decreasing inflammation and improving cerebral energy metabolism; intranasal insulin, by restoring brain insulin levels in Alzheimer's disease .Another intriguing aspect is the occurrence of variant butyrylcholinesterases with low enzyme activity in certain ethnic populations . It woulIn summary, esterase group of enzymes may be an underlying thread in the coexistence of Alzheimer's disease and diabetes mellitus."in vivo to in silico biology and back" [At present however, one cannot impute a direct cause-effect relationship among the variables discussed here , although there are epidemiological, biochemical, pathological and now computational biological leads pointing to an association. In line with emerging paradigms of nd back" , our resThe author(s) declare that they have no competing interests.GRS participated in the design of the study, interpretation of the results and prepared the manuscript. TH, SB, SP and DC participated in the design of the study, performed the bioinformatics aspects and participated in the preparation of the manuscript. AAR participated in the design of the study, guided in the bioinformatics aspects, and participated in the interpretation of the results and in the preparation of the manuscript. All authors read and approved the final manuscript.


Inconsistent findings reported in the literature contribute to the lack of complete understanding of the association of literacy with health outcomes. We evaluated the association between literacy, physiologic control and diabetes complications among adults with diabetes.A cross-sectional study of 1,002 English speaking adults with diabetes, randomly selected from the Vermont Diabetes Information System, a cluster-randomized trial of a diabetes decision support system in a region-wide sample of primary care practices was conducted between July 2003 and March 2005. Literacy was assessed by the Short-Test of Functional Health Literacy in Adults. Outcome measures included glycated hemoglobin, low density lipoprotein, blood pressure and self-reported complications.P = .88), systolic blood pressure , diastolic blood pressure , or low density lipoprotein (beta coefficent, +0.04; 95% CI, -0.27 to +0.36, P = .77. We found no association between literacy and report of diabetes complications.After adjusting for sociodemographic characteristics, duration of diabetes, diabetes education, depression, alcohol use, and medication use we did not find a significant association between literacy and glycemic control (beta coefficent,+ 0.001; 95% confidence interval [CI], -0.01 to +0.01; These findings suggest that literacy, as measured by the S-TOFHLA, is not associated with glycated hemoglobin, blood pressure, lipid levels or self-reported diabetes complications in a cross-sectional study of older adults with diabetes under relatively good glycemic control. Additional studies to examine the optimal measurement of health literacy and its relationship to health outcomes over time are needed. Navigating the US health care system requires sophisticated reading, writing, and numeracy skills that go beyond the health literacy abilities of many Americans ,2. AdultPatients with chronic conditions such as diabetes face even greater communication challenges. The complexity of diabetes care requires an informed individual who can seek, obtain, and comprehend information to engage in the management of his/her health. Health outcomes for adults with diabetes are better for those who can optimally incorporate self-management of their diabetes into their daily lives. Decreaset al.[et al.[et al.[Recent cross-sectional studies have assessed the association between literacy and diabetes care with conflicting outcomes. Williams et al. did not l.[et al. reportedl.[et al. did not l.[et al.,22 examiGiven the complexity of diabetes management, we hypothesized that adults with diabetes and limited literacy would be less likely to achieve the recommended goals for A1C, systolic blood pressure (SBP), diastolic blood pressure (DBP), and low density lipoprotein (LDL). We also hypothesized that adults with diabetes and limited literacy would report more complications related to their diabetes.This study was part of the Vermont Diabetes Information System (VDIS), a cluster-randomized trial of a diabetes decision support system in a region-wide sample of primary care practices. Characteristics of the VDIS registry, study design and data-collection procedures have been described. A fieldAt the time of the interview, a research assistant reviewed the questionnaire for completeness and asked the subjects to complete overlooked items, recorded medication use by checking actual medication containers in the home, measured height, weight, and blood pressure, and administered the Short Test of Functional Health Literacy for Adults (S-TOFHLA) and the Our study power was adequate to detect an important association between literacy and physiologic control. Given the number of subjects recruited and the observed standard deviations, we had 84% power for detecting a difference in A1C levels of 0.3% between subjects with limited versus adequate literacy. Similarly, we had 79% power to detect a 5 mmHg difference in blood pressure. For LDL, we had 83% power for a difference of 8 mg/dl.The S-TOFHLA, a 36-item, 7-minute, timed test of reading comprehension, employs the Cloze procedure, in which a word in a sentence is omitted and must be chosen from a multiple choice list. It uses passages from instructions for preparation for an upper gastrointestinal series and a section of a Medicaid application. Results are categorized into inadequate (0–16 correct answers), marginal (17–22), and adequate health literacy (23–36). The S-TOFHLA has good internal consistency  and concurrent validity compared to the long version of the TOFHLA (r = 0.91).Selected variables Table  from theth edition depression criteria on a scale of 0  to 3 (nearly every day). A score of 10 or more has been documented to have a sensitivity of 88% and a specificity of 88% for major depression[Because of the association between depression and glycemic control -28, we mepression.We obtained data about kidney disease, heart disease, and cerebrovascular disease from the Self-Administered Comorbidity Questionnaire, a modification of the Charlson Index that has moderately strong associations with a standard medical record-based co-morbidity measure. To idenThe research assistant measured height using a portable stadiometer , weight with a portable scale , and blood pressure with an automated sphygmomanometer (Omron model HEM-711). Blood pressure was obtained in the seated position in the left arm (unless contraindicated) using the cuff size recommended by the manufacturer. Three readings were obtained at five-minute intervals and averaged for the final result. We obtained each patient's most recent A1C and cholesterol levels directly from their local clinical laboratories.The primary outcomes  were analyzed as continuous variables. We analyzed literacy as both a continuous variable and a categorical variable: inadequate literacy (S-TOFHLA score 0–16), marginal literacy (S-TOFHLA score 17–22) and adequate literacy (S-TOFHA score 23–36).Regression analysis was used to measure the association between the S-TOFHLA score and each of our four outcomes  after controlling for potentially confounding patient characteristics. We performed multivariate linear regression for each primary outcome controlling for variables shown to be important clinically or in other studies,22. SpecSubjects with major cognitive impairment were excluded from the VDIS trial; nonethelWe determined the effects of literacy on self-reported retinopathy, neuropathy, gastroparesis, foot and leg ulcerations, cerebrovascular disease, and coronary artery disease, all common complications of diabetes. We performed multivariate logistic regression for each complication, controlling for age, sex, race/ethnicity, marital status, insurance, income, depression, alcohol use, diabetes education, duration of diabetes, hypertension, and medication use specific to the management of blood pressure, serum glucose, or cholesterol. We also accounted for clustering of patients with physicians. For coronary heart disease, cerebrovascular disease, and foot and leg problems related to diabetes, we also adjusted for smoking. All analyses were performed with STATA 8.2 .P < 0.001); more likely to be men ; had a lower baseline A1C ; and a higher baseline LDL  than those who completed the interview. Due to missing data on 4 subjects, we had complete questionnaire results and S-TOFHLA scores on 1002 subjects with confirmed diabetes. The demographic characteristics of the study population reflect the population of northern New England  were not reached or declined. The 7,801 non-interviewed subjects of VDIS, (which includes those who declined and those never contacted) were younger  subjects had inadequate literacy, 66 (7%) had marginal literacy, and 831 (83%) had adequate literacy  or dementia (N = 5) did not identify a significant relationship between S-TOFHLA score and A1C, LDL, or blood pressure. Likewise, excluding subjects with poor vision or other physical impairments (N = 23) revealed no significant associations between literacy and physiologic control of diabetes.More complications related to diabetes were reported by the subjects with inadequate or marginal literacy. However, the differences between the groups disappeared after adjusting for confounders. Table .After controlling for potential confounders, we did not find a significant association between literacy and health outcomes for glycemic control, blood pressure, or dyslipidemia in adults who receive diabetes care in community primary care settings. We also did not find an association between literacy and complications of diabetes. This is counter to our expectations, particularly for a study population with a chronic disease requiring self-care to achieve optimal health. Our results raise questions regarding how health literacy is assessed, how it may vary across populations, and how patients may compensate for low literacy.et al.[Our results are consistent with those of Williams et al. who repoet al. reported no significant correlation between the mean annual A1C of the child and the child's literacy level[r = 0.28; P = 0.01) after adjustment for the child's age and sex, duration of diabetes, daily insulin dose, the child's literacy score, and social class[In a study that examined the literacy level of children with type 1 diabetes and the literacy level of their mothers, Ross acy level. Howeverial class.et al.[P = 0.05) retinopathy  and cerebrovascular disease . They controlled for age, sex, race/ethnicity, education, language, insurance, social support, depressive symptoms, complications of diabetes, diabetes education, duration of diabetes, and diabetes treatment. One explanation for our conflicting results may be related to differences in the populations under study. Schillinger's study involved a younger, more ethnically diverse population with poor glycemic control (mean A1C of 8.5%). Eighty-five percent of their population reported a race/ethnicity other than white, 46% did not complete high school, 32% had no health insurance, and 93% reported an annual household income less than $20,000. Another explanation for the difference between our outcomes and those reported by Schillinger et al. may be that our measurements were not exactly the same in all domains. We used different measures to assess depression and social support and different criteria for determining the presence of complications associated with diabetes.Similarly, Schillinger et al. found thet al. report that literacy was a statistically significant effect modifier in determining how patients with diabetes did in a disease management program; the patients with lower literacy were more likely to achieve goal glycemic control[et al. reported similar baseline A1Cs between low and high literacy patients. However, in their study participation in a disease management program showed that literacy does appear to be a factor in diabetes control.Rothman c control,22. ConsOur finding of a lack of significant association between literacy and disease outcome may be because compensatory strategies may have already been implemented to accommodate literacy barriers. It may be that achievement of some goals is more dependent on practitioner action than patient self-care skills. CompareAnother possible explanation for our finding of a lack of a significant association between literacy and health outcomes is that optimal self-management of diabetes may not be solely dependent on reading ability. In addition to print literacy, health literacy includes numeracy, oral literacy, culture and context. The pubThere are several additional limitations to our study. The cross-sectional study design does not allow us to measure incident outcomes or assign cause and effect. The generalizability of the sample is limited because it comes from a single region and is racially homogenous. There is a potential self-selection bias in the population of subjects who agreed to be interviewed, who differed significantly from the non-interviewed VDIS study population who were younger, more likely to be male, had better A1Cs and worse LDLs. The younger age group may have been more likely to be working and have other competing role demands limiting their availability to engage in an interview. It is also possible that subjects who declined participation in the interview process had lower literacy skills. However, all the subjects were outpatients with a diagnosis of diabetes and are representative of patients cared for in many community based primary care settings.P values and not changed any of the conclusions.Most subjects had health insurance which can be accounted for by noting that the patients were recruited from primary care practices where they were receiving care, half were Medicare eligible, and Vermont has a low proportion of uninsured. The study population had relatively good glycemic control with almost half having an A1C < 7 %. The impact of literacy may be greater in a population with poorer glycemic control. Cognition is likely related to literacy and we did not specifically assess cognitive status but relied on exclusion criteria for the VDIS study which eliminated people with significant cognitive impairment. Data about diabetes complications were obtained by self-report and not verified by chart review. This may have resulted in some inaccuracies depending on a person's interpretation of the phrases chosen to query the presence of complications such as "problems with vision related to diabetes." Lastly, we note that multiple testing was performed; correction for this would have resulted in larger Our study suggests that literacy, as measured by the S-TOFHLA, is not associated with A1C, LDL, or BP in a cross-sectional study of older adults with diabetes under relatively good glycemic control. The common complications of diabetes are not associated with limited literacy in this population. Additional studies to examine the optimal measurement of health literacy and its relationship to health outcomes are needed.The author(s) declare that they have no competing interests.NSM made substantial contributions to analysis and interpretation of data, provided important intellectual content, and was involved in drafting and revising the manuscript. CDM made substantial contributions to conception and design; acquisition, analysis and interpretation of data; provided intellectual content and contributed to critical revision of the manuscript. BL made substantial contributions to conception and design; acquisition, analysis and interpretation of data; provided intellectual content and contributed to critical revision of the manuscript. All authors read and approved the final version of the manuscript.The pre-publication history for this paper can be accessed here: