Upregulation of the Mevalonate Pathway through EWSR1-FLI1/EGR2 Regulatory Axis Confers Ewing Cells Exquisite Sensitivity to Statins.

Ewing sarcoma (EwS) is an aggressive primary bone cancer in children and young adults characterized by oncogenic fusions between genes encoding FET-RNA-binding proteins and ETS transcription factors, the most frequent fusion being EWSR1-FLI1. We show that EGR2, an Ewing-susceptibility gene and an essential direct target of EWSR1-FLI1, directly regulates the transcription of genes encoding key enzymes of the mevalonate (MVA) pathway. Consequently, Ewing sarcoma is one of the tumors that expresses the highest levels of mevalonate pathway genes. Moreover, genome-wide screens indicate that MVA pathway genes constitute major dependencies of Ewing cells. Accordingly, the statin inhibitors of HMG-CoA-reductase, a rate-limiting enzyme of the MVA pathway, demonstrate cytotoxicity in EwS. Statins induce increased ROS and lipid peroxidation levels, as well as decreased membrane localization of prenylated proteins, such as small GTP proteins. These metabolic effects lead to an alteration in the dynamics of S-phase progression and to apoptosis. Statin-induced effects can be rescued by downstream products of the MVA pathway. Finally, we further show that statins impair tumor growth in different Ewing PDX models. Altogether, the data show that statins, which are off-patent, well-tolerated, and inexpensive compounds, should be strongly considered in the therapeutic arsenal against this deadly childhood disease.

Oncogenic chimeric transcription factors drive tumor-specific transcription, processing, and translation of silent genomic regions.

Many cancers are characterized by gene fusions encoding oncogenic chimeric transcription factors (TFs) such as EWS::FLI1 in Ewing sarcoma (EwS). Here, we find that EWS::FLI1 induces the robust expression of a specific set of novel spliced and polyadenylated transcripts within otherwise transcriptionally silent regions of the genome. These neogenes (NGs) are virtually undetectable in large collections of normal tissues or non-EwS tumors and can be silenced by CRISPR interference at regulatory EWS::FLI1-bound microsatellites. Ribosome profiling and proteomics further show that some NGs are translated into highly EwS-specific peptides. More generally, we show that hundreds of NGs can be detected in diverse cancers characterized by chimeric TFs. Altogether, this study identifies the transcription, processing, and translation of novel, specific, highly expressed multi-exonic transcripts from otherwise silent regions of the genome as a new activity of aberrant TFs in cancer.

STAG2 mutations alter CTCF-anchored loop extrusion, reduce cis-regulatory interactions and EWSR1-FLI1 activity in Ewing sarcoma.

STAG2, a cohesin family gene, is among the most recurrently mutated genes in cancer. STAG2 loss of function (LOF) is associated with aggressive behavior in Ewing sarcoma, a childhood cancer driven by aberrant transcription induced by the EWSR1-FLI1 fusion oncogene. Here, using isogenic Ewing cells, we show that, while STAG2 LOF profoundly changes the transcriptome, it does not significantly impact EWSR1-FLI1, CTCF/cohesin, or acetylated H3K27 DNA binding patterns. In contrast, it strongly alters the anchored dynamic loop extrusion process at boundary CTCF sites and dramatically decreases promoter-enhancer interactions, particularly affecting the expression of genes regulated by EWSR1-FLI1 at GGAA microsatellite neo-enhancers. Down-modulation of cis-mediated EWSR1-FLI1 activity, observed in STAG2-LOF conditions, is associated with enhanced migration and invasion properties of Ewing cells previously observed in EWSR1-FLI1low cells. Our study illuminates a process whereby STAG2-LOF fine-tunes the activity of an oncogenic transcription factor through altered CTCF-anchored loop extrusion and cis-mediated enhancer mechanisms.

Modulation of Arterial Stiffness Gradient by Acute Administration of Nitroglycerin.

Background: Physiologically, the aorta is less stiff than peripheral conductive arteries, creating an arterial stiffness gradient, protecting microcirculation from high pulsatile pressure. However, the pharmacological manipulation of arterial stiffness gradient has not been thoroughly investigated. We hypothesized that acute administration of nitroglycerin (NTG) may alter the arterial stiffness gradient through a more significant effect on the regional stiffness of medium-sized muscular arteries, as measured by pulse wave velocity (PWV). The aim of this study was to examine the differential impact of NTG on regional stiffness, and arterial stiffness gradient as measured by the aortic-brachial PWV ratio (AB-PWV ratio) and aortic-femoral PWV ratio (AF-PWV ratio). Methods: In 93 subjects (age: 61 years, men: 67%, chronic kidney disease [CKD]: 41%), aortic, brachial, and femoral stiffnesses were determined by cf-PWV, carotid-radial (cr-PWV), and femoral-dorsalis pedis artery (fp-PWV) PWVs, respectively. The measurements were repeated 5 min after the sublingual administration of NTG (0.4 mg). The AB-PWV and AF-PWV ratios were obtained by dividing cf-PWV by cr-PWV or fp-PWV, respectively. The central pulse wave profile was determined by radial artery tonometry through the generalized transfer function. Results: At baseline, cf-PWV, cr-PWV, and fp-PWV were 12.12 ± 3.36, 9.51 ± 1.81, and 9.71 ± 1.89 m/s, respectively. After the administration of NTG, there was a significant reduction in cr-PWV of 0.86 ± 1.27 m/s (p < 0.001) and fp-PWV of 1.12 ± 1.74 m/s (p < 0.001), without any significant changes in cf-PWV (p = 0.928), leading to a significant increase in the AB-PWV ratio (1.30 ± 0.39 vs. 1.42 ± 0.46; p = 0.001) and AF-PWV ratio (1.38 ± 0.47 vs. 1.56 ± 0.53; p = 0.001). There was a significant correlation between changes in the AF-PWV ratio and changes in the timing of wave reflection (r = 0.289; p = 0.042) and the amplitude of the heart rate-adjusted augmented pressure (r = - 0.467; p < 0.001). Conclusion: This study shows that acute administration of NTG reduces PWV of muscular arteries (brachial and femoral) without modifying aortic PWV. This results in an unfavorable profile of AB-PWV and AF-PWV ratios, which could lead to higher pulse pressure transmission into the microcirculation.

The Obesity-Fertility Protocol: a randomized controlled trial assessing clinical outcomes and costs of a transferable interdisciplinary lifestyle intervention, before and during pregnancy, in obese infertile women.

BACKGROUND: Obesity in infertile women increases the costs of fertility treatments, reduces their effectiveness and increases significantly the risks of many complications of pregnancy and for the newborn. Studies suggest that even a modest loss of 5-10 % of body weight can restore ovulation. However, there are gaps in knowledge regarding the benefits and cost-effectiveness of a lifestyle modification program targeting obese infertile women and integrated into the fertility clinics. This study will evaluate clinical outcomes and costs of a transferable interdisciplinary lifestyle intervention, before and during pregnancy, in obese infertile women. We hypothesize that the intervention will: 1) improve fertility, efficacy of fertility treatments, and health of mothers and their children; and 2) reduce the cost per live birth, including costs of fertility treatments and pregnancy outcomes. METHODS/DESIGN: Obese infertile women (age: 18-40 years; BMI ≥30 kg/m(2) or ≥27 kg/m(2) with polycystic ovary syndrome) will be randomised to either a lifestyle intervention followed by standard fertility treatments after 6 months if no conception has been achieved (intervention group) or standard fertility treatments only (control group). The intervention and/or follow-up will last for a maximum of 18 months or up to the end of pregnancy. Evaluation visits will be planned every 6 months where different outcome measures will be assessed. The primary outcome will be live-birth rates at 18 months. The secondary outcomes will be sub-divided into four categories: lifestyle and anthropometric, fertility, pregnancy complications, and neonatal outcomes. Outcomes and costs will be also compared to similar women seen in three fertility clinics across Canada. Qualitative data will also be collected from both professionals and obese infertile women. DISCUSSION: This study will generate new knowledge about the implementation, impacts and costs of a lifestyle management program in obese infertile women. This information will be relevant for decision-makers and health care professionals, and should be generalizable to North American fertility clinics. TRIAL REGISTRATION: ClinicalTrials.gov NCT01483612. Registered 25 November 2011.

Alterations in metabolic profile occur in normal-weight and obese men during the Ramadan fast despite no changes in anthropometry.

We examined the variations in eating behavior, appetite ratings, satiety efficiency, energy expenditure, anthropometric and metabolic profile markers prior to, during as well as 1 and 4 months after Ramadan in normal-weight and obese men. Anthropometric, energy expenditure (indirect calorimetry and accelerometry), metabolic (fasting blood sample), appetite (visual analogue scales), and eating behavior (Three-Factor Eating Questionnaire) measurements were performed in 10 normal-weight (age: 25.2 ± 4.7 years; BMI: 24.4 ± 1.9 kg/m(2)) and 10 obese (age: 27.0 ± 4.5 years; BMI: 34.8 ± 3.7 kg/m(2)) men. The satiety quotient (SQ) was calculated 180 minutes after breakfast consumption. All anthropometric variables, as well as resting and total energy expenditure, were greater in obese compared to normal-weight participants (P = 0.02-0.0001). Similarly, obese participants had greater triglycerides, insulin, and homeostatic model assessment-insulin resistance concentrations (P = 0.02-0.002). Greater apolipoprotein B, glucose, total cholesterol, and low-density lipoprotein concentrations were noted during Ramadan (P = 0.04-0.0001). Dietary restraint scores were also greater during Ramadan (P = 0.0001). No differences in anthropometry, other metabolic profile markers, energy expenditure, appetite ratings, and SQ were noted across sessions. Lastly, changes in anthropometric measurements correlated with delta metabolic profile markers, as well as changes in disinhibition eating behavior trait and dietary restraint scores. The Ramadan fast led to increases in certain metabolic profile markers despite no changes in appetite and anthropometry.

Antagonism pattern detection between microRNA and target expression in Ewing's sarcoma.

MicroRNAs (miRNAs) have emerged as fundamental regulators that silence gene expression at the post-transcriptional and translational levels. The identification of their targets is a major challenge to elucidate the regulated biological processes. The overall effect of miRNA is reflected on target mRNA expression, suggesting the design of new investigative methods based on high-throughput experimental data such as miRNA and transcriptome profiles. We propose a novel statistical measure of non-linear dependence between miRNA and mRNA expression, in order to infer miRNA-target interactions. This approach, which we name antagonism pattern detection, is based on the statistical recognition of a triangular-shaped pattern in miRNA-target expression profiles. This pattern is observed in miRNA-target expression measurements since their simultaneously elevated expression is statistically under-represented in the case of miRNA silencing effect. The proposed method enables miRNA target prediction to strongly rely on cellular context and physiological conditions reflected by expression data. The procedure has been assessed on synthetic datasets and tested on a set of real positive controls. Then it has been applied to analyze expression data from Ewing's sarcoma patients. The antagonism relationship is evaluated as a good indicator of real miRNA-target biological interaction. The predicted targets are consistently enriched for miRNA binding site motifs in their 3'UTR. Moreover, we reveal sets of predicted targets for each miRNA sharing important biological function. The procedure allows us to infer crucial miRNA regulators and their potential targets in Ewing's sarcoma disease. It can be considered as a valid statistical approach to discover new insights in the miRNA regulatory mechanisms.

Intergenerational cycle of obesity and diabetes: how can we reduce the burdens of these conditions on the health of future generations?

Prepregnancy overweight or obesity and excessive gestational weight gain have been associated with increased risk of maternal and neonatal complications. Moreover, offspring from obese women are more likely to develop obesity, diabetes mellitus, and cardiovascular diseases in their lifetime. Gestational diabetes mellitus (GDM) is one of the most common complications associated with obesity and appears to have a direct impact on the future metabolic health of the child. Fetal programming of metabolic function induced by obesity and GDM may have intergenerational effect and thus perpetuate the epidemic of cardiometabolic conditions. The present paper thus aims at discussing the impact of maternal obesity and GDM on the developmental programming of obesity and metabolic disorders in the offspring. The main interventions designed to reduce maternal obesity and GDM and their ability to break the vicious circle that perpetuates the transmission of obesity and metabolic conditions to the next generations are also addressed.

Neuromuscular strategies in the paretic leg during curved walking in individuals post-stroke.

Reduced flexibility over the neuromotor control of paretic leg muscles may impact the extent to which individuals post-stroke modulate their muscle activity patterns to walk along curved paths. The purpose of this study was to compare lower-limb movements and neuromuscular strategies in the paretic leg of individuals with stroke with age-matched controls during curved walking. Participants walked at their preferred walking velocity along four different paths of increasing curvature, while lower-limb kinematics and muscle activity were recorded. A second group of able-bodied individuals walked along the four paths, matching the walking speed of the stroke group. The stroke group showed reduced lower-limb joint excursion and disordered modulation of foot pressure during curved walking, accompanied by reduced modulation of muscle activity patterns. In the inner leg of the curve in control subjects, the posteromedial muscles (medial gastrocnemius and medial hamstrings) showed decreased electromyographic amplitude as path curviture increased. Conversely, activity of the posterolateral musculature of the outer leg was decreased with increasing path curvature. Activity in the tibialis anterior and gluteus medius was also modulated with path curvature. However, in the stroke group, we found reduced modulation of muscle activity in the paretic leg during curved walking. The extent of modulation was also associated with the level of physical impairment due to stroke. The results of this study provide further knowledge about neuromuscular control of locomotor adaptations post-stroke.

The mechanical relationship between the rearfoot, pelvis and low-back.

The purpose of this study was first to investigate whether foot pronation (measured as calcaneal eversion) induced an anterior tilt of the pelvis and increased the degree of lumbar lordosis. Second the study investigated whether foot supination (measured as calcaneal inversion) induced a posterior pelvic tilt and a decreased lumbar lordosis. Participants placed their feet in 18 different foot positions while standing on a rigid platform. Seven of these positions ranged from 15 degrees of foot eversion to 15 degrees of foot inversion and 11 positions ranged from 40 degrees of external foot rotation to 40 degrees of internal foot rotation. Pelvic tilt and lumbar lordosis were estimated using a 3D motion analysis system. Foot pronation and supination did not have a significant relationship with pelvic tilt (r=0.3) and lumbar lordosis (r=0.05). Internally rotating the legs caused the pelvis to tilt anteriorly and externally rotating the legs caused the pelvis to tilt posteriorly (r=0.58). There was no relationship between leg rotation and lumbar lordosis (r=0.24). Since the effects of pelvic tilt on the lumbar spine were only noticeable when pelvic tilt was exaggerated beyond values seen this study it seems unlikely that there is a link between induced foot pronation and an increase in lumbar lordosis.

Psychosocial risk factors for depressive symptoms after the AZF chemical factory explosion in Toulouse, France.

BACKGROUND: On 21 September 2001, a huge explosion occurred in a chemical plant in Toulouse. The hypothesis of the study was that the level of depressive symptoms after an industrial disaster would be related to the intensity of exposure and the characteristics of the exposed population, as well as to the consequences of the disaster during the following months. METHODS: A random sample of the population living close to the plant at the time of the explosion was included in a cross-sectional study, and 811 persons aged > 18 years were interviewed at home. The depressive symptoms score was analysed by gender in relation to characteristics of the population before the explosion, immediate exposure to the explosion and post-trauma factors. RESULTS: The mean depressive symptoms scores (± SD) 18 months after the explosion were 17.8 (± 1) in women and 13.5 (± 1) in men. Age > 45 years and psychiatric treatment in the previous year; high immediate exposure (proximity to the site at the time of the explosion < 2500 m); and post-trauma factors such as financial difficulties or physical sequelae during the months after the disaster were related to a higher depressive symptoms score in both men and women. CONCLUSION: In the population living near the site of an industrial explosion, individual vulnerability, exposure and post-trauma factors were associated with depressive symptoms. All three sets of factors need to be taken into account when planning a response to a disaster and reducing the psychological aftermath.

Low body fat and high cardiorespiratory fitness at the onset of the freshmen year may not protect against weight gain.

The purpose of this study was to examine the effects of pre-university adiposity and physical fitness on changes of body weight and adiposity during the freshmen year. Twenty-nine freshmen (sixteen females and thirteen males) completed the study. Body weight and composition (dual-energy X-ray absorptiometry), waist circumference (WC), energy intake (7 d food diary) and activity-related energy expenditure (accelerometry) were measured in September, December and at the end of March. Peak oxygen uptake (VO2peak) was assessed at baseline only. Significant increases in body weight (1.9 (SD 2.0) kg, P < 0.05), BMI (0.6 (SD 0.7) kg/m2, P < 0.05), WC (2.7 (SD 3.0) cm, P < 0.05) and % body fat (BF) (3.1 (SD 2.3) %, P < 0.01) were noted in males, especially over the course of the first semester. No significant changes were observed in females. Results from correlation analyses showed that, baseline %BF was negatively associated with changes in body weight (r - 0.53, P < 0.01) and %BF (r - 0.41, P < 0.05) over the academic year. Baseline %BF predicted 27 % (P < 0.05) of the change in weight. Alcohol intake explained 34 % (P < 0.01) and 17 % (P < 0.05) of the changes in WC and %BF, respectively. The change in body weight and %BF were also positively associated with baseline VO2peak (r 0.51, P < 0.01; r 0.48, P < 0.01, respectively) while dietary restraint was negatively related to the changes in %BF (r - 0.43, P < 0.05). In summary, lower pre-university adiposity, higher VO2peak and higher alcohol intake are associated with greater changes in adiposity and body weight during the freshmen year.

Physical activity is a confounding factor of the relation between eating frequency and body composition.

BACKGROUND: It has been shown that eating frequency (EF) is related to body composition in women, but the results are inconclusive. These inconsistent findings could be due to the influence of additional factors such as physical activity. OBJECTIVE: We aimed to investigate the relation between EF and body composition in premenopausal women and to explore the effect of physical activity energy expenditure (PAEE) and physical fitness on that association. DESIGN: Eighty-five premenopausal women [x +/- SD age: 49.9 +/- 2.0 y; body mass index (in kg/m(2)): 23.2 +/- 2.2] were studied at the onset of a prospective observational study. Seven-day food diaries were used to measure energy intake and EF. Body composition (measured with dual-energy X-ray absorptiometry), physical fitness (measured by the peak oxygen consumption), and PAEE (measured by using an accelerometer) were also measured. RESULTS: Mean EF was 4.6 +/- 0.9 eating occasions/d. A significant positive correlation was found between EF and energy intake (r = 0.31, P < 0.01). Moreover, EF was negatively correlated with body mass index (r = -0.25, P < 0.05), waist circumference (r = -0.32, P < 0.01), percentage body fat (r = -0.26, P < 0.05), and fat mass (r = -0.27, P < 0.05). The associations between adiposity and EF were no longer significant after correction for PAEE and peak oxygen consumption. CONCLUSION: The relation between EF and body composition could be mediated by PAEE and physical fitness.

A brief intervention for fatigue management in breast cancer survivors.

The purpose of this randomized control trial was to verify the effectiveness of a brief group intervention that combines stress management psycho-education and physical activity (ie, independent variable) intervention in reducing fatigue and improving energy level, quality of life (mental and physical), fitness (VO 2submax), and emotional distress (ie, dependent variables) in breast cancer survivors. This study applied Lazarus and Folkman stress-coping theoretical framework, as well as Salmon's unifying theory of physical activity. Eighty-seven French-speaking women who had completed their treatments for nonmetastatic breast cancer at a university hospital in Quebec City, Canada, were randomly assigned to either the group intervention (experimental) or the usual-care (control) condition. Data were collected at baseline, postintervention, and at 3-month follow-up. The 4-week group intervention was cofacilitated by 2 nurses. Results showed that participants in the intervention group showed greater improvement in fatigue, energy level, and emotional distress at 3-month follow-up, and physical quality of life at postintervention, compared with the participants in the control group. These results suggest that a brief psycho-educational group intervention focusing on active coping strategies and physical activity is beneficial to cancer survivors after breast cancer treatments.

Adaptation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) into French-Canadian and English-Canadian.

BACKGROUND: The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is the first disease-specific instrument for assessing patient-reported symptoms, functioning and quality of life (QoL) in pulmonary arterial hypertension (PAH). OBJECTIVES: To create and validate French-Canadian (FC) and English-Canadian (EC) language versions of the CAMPHOR. METHODS: A translation panel (for the FC version) and lay panels (for both versions) were convened to adapt the questionnaires (dual-panel methodology). Subsequently, these new questionnaires were field-tested in 15 FC PAH and 15 EC PAH patients. Finally, in a postal validation study, the new language versions of the CAMPHOR underwent psychometric evaluation in 41 FC and 52 EC PAH patients to test for reliability and validity. RESULTS: The FC and EC field-test interview participants found the questionnaires relevant, comprehensible and easy to complete. Psychometric analyses showed that the FC and EC adaptations were successful. High test-retest coefficients for the scales after controlling for change in respondent's QoL (FC: 0.92 to 0.96; EC: 0.85 to 0.99) indicated a high degree of reliability. The FC and EC CAMPHOR scales had good internal consistency (Cronbach's alpha coefficients 0.90 to 0.92 and 0.88 to 0.92, respectively). Predicted correlations with the Nottingham Health Profile provided evidence of the construct validity of the FC and EC scales. The FC and EC adaptations also showed known groups validity. CONCLUSIONS: The FC and EC adaptations of the CAMPHOR have been shown to be reliable and valid for measures of health-related QoL and QoL in PAH, and thus can be recommended for use in clinical studies and routine practice in PAH.

Hearing status after an industrial explosion: experience of the AZF explosion, 21 September 2001, France.

OBJECTIVES: Following the explosion of a chemical plant in France, a study was conducted to analyse the relationship between hearing thresholds and distance from the explosion based on post- and pre-blast audiometric data, and to describe the functional symptoms and visits for hearing problems. METHODS: Audiometric tests with standard procedure of 511 workers of a company located near the explosion were proposed and conducted by the occupational medicine department after the explosion. Past occupational noise exposure, past medical history of ear problems, distance from the explosion, functional symptoms and visits for hearing problems following explosion and results of past audiometric tests if available were collected. Workers were classified as "exposed" or "less exposed" according to the distance from the explosion. Mean decibel threshold shifts for each ear were analysed by frequency with Student's t test and by multiple linear regression taking into account confounding factors. RESULTS: Of a total of 425 (83%) of the firm's workers who participated in the study, 49% had received an audiometric test before the explosion. Hearing shift between pre- and post-explosion audiograms was significantly greater for the "exposed" group than for the "less exposed" one at 2,000 and 4,000 Hz (P < 0.05, P < 0.001, respectively) and borderline at 6,000 Hz (P = 0.09) for the right ear and at 2,000 (P < 0.01), 6,000 and 8,000 Hz (P < 0.05) for the left ear. Among those of the "exposed" workers who reported any functional symptom following the explosion, 45% did not visit an ENT specialist despite these signs. CONCLUSIONS: The study demonstrated statistically significant hearing shift from 2,000 to 6,000 Hz in relation with distance from the explosion and showed that even when functional symptoms were present, people did not necessarily seek medical advice. Screening for hearing loss should be recommended for people most exposed to excess acoustic pressure, in order to offer them prevention advice.

Mesenchymal stem cell features of Ewing tumors.

The cellular origin of Ewing tumor (ET), a tumor of bone or soft tissues characterized by specific fusions between EWS and ETS genes, is highly debated. Through gene expression analysis comparing ETs with a variety of normal tissues, we show that the profiles of different EWS-FLI1-silenced Ewing cell lines converge toward that of mesenchymal stem cells (MSC). Moreover, upon EWS-FLI1 silencing, two different Ewing cell lines can differentiate along the adipogenic lineage when incubated in appropriate differentiation cocktails. In addition, Ewing cells can also differentiate along the osteogenic lineage upon long-term inhibition of EWS-FLI1. These in silico and experimental data strongly suggest that the inhibition of EWS-FLI1 may allow Ewing cells to recover the phenotype of their MSC progenitor.

Assessing post-disaster consequences for health at the population level: experience from the AZF factory explosion in Toulouse.

BACKGROUND: A major explosion occurred in the AZF chemical factory in Toulouse in September 2001. A comprehensive programme of epidemiological surveillance was set up. OBJECTIVES: To present an overview of the programme and discuss the methods and potential utility of post-disaster epidemiology. The programme had three objectives: (1) to analyse comprehensively the short-term and long-term effects of air, water and secondary soil pollution on health; (2) to identify health problems needing special attention; and (3) to investigate the long-term direct and indirect effects on the population's health. METHODS: The programme was organised through three committees: (1) a scientific committee, (2) an executive programme committee and (3) an institutional committee which aimed to facilitate exchanges between the epidemiologists, the regional authorities, the population and the media. As the catastrophe was an industrial disaster that had a major effect on workers and companies, and also caused severe damage to many schools and buildings all over the city, routine and ad hoc surveillance systems were used and three specific ad hoc questionnaire surveys in workers, schoolchildren and the general population were planned. RESULTS AND CONCLUSIONS: Although the routine surveillance systems had limitations, several sources provided useful information for public health decisions and were found to be concordant with ad hoc epidemiological studies. Defining a victim was central to the choice of a programme design based on an approach either to victims of the disaster or to the entire population in the surrounding region. Anticipation and preparation for such disasters are thus required.

Health-related quality of life in morbid obesity.

BACKGROUND: In order to evaluate the impact of severe obesity and its treatment on quality of life (QoL), it would be important to first identify the areas of QoL most likely to be affected by the disease. METHODS: We first constructed a list of 187 items potentially related to QoL of patients with morbid obesity. From this list, consecutive candidates for bariatric surgery were asked to identify what they felt were the most significant items and to grade their importance. The item impact was determined from the proportion of patients who identified it as important, and the mean importance score attributed to this item (impact score = frequency X importance). RESULTS: 100 patients (68 female; mean body mass index 51.5 kg/m(2); mean age 42) were interviewed. Overall, the impact of morbid obesity was more important in women than in men. The areas of impairment were very similar in both groups, with the important difference that women ranked their dissatisfaction with physical appearance higher than men. The items having the most important impact on QoL clustered into 7 domains: 1) activity/mobility; 2) symptoms; 3) personal hygiene/clothing; 4) emotions; 5) social interactions; 6) sexual life; and 7) eating behavior. CONCLUSION: The impact of morbid obesity on QoL is not limited to the activity/mobility domain. Morbid obesity contributes to the impairment of all domains of what is usually referred to as "health-related quality of life".