Cavotricuspid isthmus (CTI) ablation is the treatment of choice in preventing recurrences of typical atrial flutter (AFl). However, little is known about long-term quality of life (QoL) after CTI ablation.From 01/2003 to 05/2005, 94 patients who consecutively underwent typical AFl ablation were included in the study. An SF-36 health questionnaire was self-administered before ablation and at follow-up. Transformed scores were calculated, adjusted for age and sex and then normalized and standardized for the Spanish population. Additionally, the minimal important differences (MID) were calculated to assess the smallest change in QoL that patients perceived as positive. A linear regression model was constructed to assess long-term QoL predictors. All SF-36 scales were lower than Spanish population scores. After a mean (SD) follow-up of 6.25 (0.5) years, all scales, except Bodily Pain, were higher than baseline. There was a significant difference for Physical Role , Vitality  and Mental Health . However, only Physical Role achieved the criteria for MID. Recurrence of AFl, basal QoL, history of diabetes mellitus, atrial fibrillation and oral anticoagulation were predictors of long-term QoL.CTI ablation provides a significant improvement in long-term QoL for the dimensions of Physical Role, Vitality and Mental Health, although the smallest positive change that patients perceive as positive was only observed for Physical Role. Previous diabetes mellitus, atrial fibrillation, oral anticoagulation, basal QoL and AFl recurrence were determinants of a worse long-term QoL. The anterior barrier of the activation wave is formed by the tricuspid annulus, while the posterior barrier is formed by the an valve . The cavan valve -3. The san valve . Howeveran valve . Our objA total of 94 patients admitted consecutively to our institution for typical AFl ablation between January 2003 and May 2005 were included in the study.The inclusion criteria were: a) aged over 18 years, b) the presence of one or more episodes of documented AFl in the previous six months, and c) a demonstration by electrophysiological study of either CTI-dependent AFl or CTI permeability, accompanied by an electrocardiogram taken during a clinical episode consistent with typical AFl in those cases in which the procedure was performed in sinus rhythm.The exclusion criteria were: a) atypical AFl (non CTI-dependent), b) patients with an implantable cardiac defibrillator (ICD), c) patients who had undergone cardiac surgery or invasive cardiac procedures (coronary angioplasty or cardiac stimulation devices) in the previous month, and d) those patients with a life expectancy of less than one year or patients who were unable to complete the questionnaire.All 94 patients included in the study self-administered the SF-36 during the 24–48 hours pre-ablation procedure and at follow-up. The mean (SD) follow-up was 6.26 (0.5) years and was completed for 96.8% of patients.We use the Spanish version 2.0 of the SF-36 and modified the standard form to include a longer follow-up period.After all questionnaires had been administered, the 36 items were grouped and coded according to the SF-36 Health Survey manual and its interpretation guide .A linear transformation of all scores was performed on a scale from 0 to 100, with 0 representing the worst health status on that scale or dimension, and 100 the best health status.All dimensions were then standardized and normalized for the Spanish population, adjusted for age and sex, such that the reference values have a mean (SD) of 50 (10). This allowed the results to be compared directly with the reference population, and for scores above or below 50 to indicate better or worse health, respectively, than the average for the Spanish general population. The Physical and Mental Summary Components (PCS and MCS) were also calculated, each of which was also normalized to an overall population mean (SD) of 50 (10).In addition, to quantify the magnitude of the change in health status, the effect size (ES) and the standardized response mean (SRM) were calculated for each dimension ,9. The EThe ES and SRM translate the changes into a standard unit of measurement that allows the different measures to be compared: a) <0.20: very small amount of change, b) from 0.20 to 0.5: small amount of change, c) from 0.6 to 0.80: moderate magnitude of change, d) > 0.80: large amount of change.Another way to quantify the ES is to compare it with the minimal important difference (MID) -12. The d: intraclass correlation coefficient of the differences between baseline and follow-up for each dimension.rb: baseline SD of each dimension.SDd: SD of the difference between the baseline and follow-up groups.SDThe ceiling effect and the floor effect were determined for each dimension. The floor value is considered to be the percentage of patients who have the lowest value and the ceiling value is the percentage of patients with the highest value. The floor or ceiling effect is present if more than 15% of patients reach floor or ceiling values within each dimension.Finally, the long-term QoL predictors were evaluated.Quantitative variables were expressed in terms of mean and standard deviation if normally distributed, or as within median and interquartile range if the data were clearly skewed. Qualitative variables were expressed as frequencies and percentages.T test and the Mann–Whitney U test were used to compare the dimensions of the SF-36, according to whether or not normality assumptions were met. A Levene test (homogeneity of variances) and Kolmogorov–Smirnov test  were used to assess the nature of the distribution of each variable. A Wilcoxon rank sum test was used to compare the values of the transformed scores between baseline and follow-up dimensions.The statistical Student’s stepAIC function (library MASS) and the lm function (basic library). The statistical criterion AIC was used, so the lower the value, the better the statistical model. Using this model we identified, based on AIC statistic values, the group which includes all predictors that best explains the dependent variables and that reaches statistical significance, independently of the individual statistical significance of each variable. Both libraries are freely available on the CRAN-R website.The factors related to long-term QoL (PCS and MCS at follow-up) were determined by using a multiple linear regression model, using the All analyses were performed using SPSS Statistics 17.0  and R .All patients gave written informed consent and this work has the approval of the Clinical Research Ethics Committee of Galicia.Most of the patients were male (82%). The mean (SD) age was 64 11) years. A total of 44% of patients had a history of atrial fibrillation (AF), 50% received antiarrhythmic drugs (AAD) and 55 (59%) received oral anticoagulation (OAC). The presence of diabetes mellitus (DM) was common (20%), 10 patients (11%) had a history of myocardial infarction, 18 (19%) of heart failure and 21% suffered from Chronic Obstructive Pulmonary Disease (COPD). We documented a component of tachycardiomyopathy in 17 (18%) patients. Table 1 years. During follow-up, 16 patients died, three were lost to follow-up and one patient developed a dementia, so was unable to complete the SF-36 questionnaire. Therefore, 74 patients completed the SF-36 at follow-up. The mean (SD) age was 70 (11) years and 82% were male. Hypertension was frequent (68%), 20% suffered from DM and 38% from osteoarthritis. The presence of heart failure and COPD was detected in 12% of patients. During follow-up, 51% of patients developed AF and in 38% of cases the AF was chronic. AFl recurrence was documented in 15 (16%) patients, of whom 14 underwent a new ablation procedure and one patient underwent electrical cardioversion.At baseline, mean scores for all dimensions were lower than mean scores for the Spanish population . The highest score was obtained for Bodily Pain Table . For PhyAt follow-up, mean scores for all dimensions were higher than those obtained at baseline, except for Bodily Pain, but all were lower than the Spanish population mean scores Table .With respect to the differences between baseline and long term QoL, there was a large difference (greater than eight) for Physical Role (p <0.001), a small difference (between four and six) for Mental Health (p = 0.001) and a very small difference (less than four) for Vitality (p <0.001) and Bodily Pain (p = 0.003); the last of these had the lowest score at follow-up. Table The smallest change in health status perceived by the patient was evaluated using the differences between the QoL at baseline and at follow-up in relation to ES and the SRM. The values were similar for both indicators. Physical Role was the only dimension that achieved the threshold established for MID because the change (0.67 for ES and 0.63 for SRM) exceeded the minimum required to be clinically perceived by the patient on the Physical Role (0.65 for ES and 0.59 for SRM). Table At baseline and at follow-up a ceiling effect was determined for Physical Role, Bodily Pain, Social Function and Emotional Role, and a floor effect was determined for Physical Role and Emotional Role, so more questions would probably be required to evaluate these dimensions more effectively in order to assess changes with regard to the baseline scores after typical AFl ablation. Both Role dimensions often have a ceiling or floor effect in the published literature ,14. The Factors related to long-term QoL were evaluated using two multiple linear regression models in which the dependent variables were the PCS and MCS, and the independent variables were the baseline PCS and MCS, the history of DM, AF, OAC, heart failure, COPD, osteoarthritis, the occurrence of AF during follow-up and AFl recurrence. The set of variables that best explained the PCS were the baseline PCS, AFl recurrence, previous AF, OAC and DM (p <0.001) Table . For theThe main finding of our study was the improvement of QoL over a long-term period in a group of patients with typical AFl undergoing CTI ablation. This is, to the best of our knowledge, the first study to assess QoL in this population over a long-term period such as this (more than five years) and that used MID to assess QoL changes perceived by the patient. The SF-36 questionnaire is an extensively validated generic QoL measure and has been used in the study of numerous health conditions, including AFl . Unlike Patients had a low score for all SF-36 questionnaire dimensions at baseline. After a long-term follow-up, all dimensions were higher and Physical Role, Vitality and Mental Health significantly improved; however, we only observed a significant MID for Physical Role. This is very important because it indicated that improvements in QoL after CTI ablation are not in fact perceived by the patient in long-term follow-up, except for Physical Role, suggesting that this dimension is particularly affected in AFl and CTI ablation provides an improvement after several years, although, because of its ceiling effect, we cannot know exactly the magnitude of improvement on QoL.The baseline dimensions were very low and, probably, the existence of comorbidity factors such as DM, heart failure and osteoarthritis partly contributed to these findings. These chronic afflictions have an impact on QoL and, in fact, chronic diseases such as arthritis or osteoarthritis may condition a nine-point difference for the Physical Function dimension, and others, such as DM or heart failure, can explain a difference of up to 13 points .Previous studies that assessed the basal QoL showed similar results ,17. The The basal dimension with the highest score was Bodily Pain, which seems not to be very important role for patients with AFl; indeed, the most common symptoms associated with AFl are palpitations, shortness of breath or occasionally heart failure and, rarely, chest pain .At follow-up, scores were higher than baseline scores for all dimensions of health, except for Bodily Pain, the worst scores for which could be explained by an increase in age-related noncardiac comorbidities such as, for example, osteoarthritis. There was a significant difference between follow-up and baseline scores for Physical Role, Vitality and Mental Health. The improvement for Mental Health and Vitality is important because these dimensions showed neither a ceiling nor a floor effect, which means that the SF-36 questionnaire can reliably perceive positive or negative changes for these dimensions. Moreover, Vitality is an important dimension because it represents the physical and mental aspects of health. However, all scores were low in relation to the Spanish general population. It is possible that associated comorbidities could explain this finding.Several studies in the literature ,17,21-23The main determinants of long-term QoL that we found were the baseline QoL, AFl recurrence, the previous DM, OAC and AF. AFl recurrence often presents with high ventricular rates, which makes it a very symptomatic arrhythmia; it is more difficult to achieve an appropriate rate control using antiarrhythmic drugs. That is why this arrhythmia has an important impact on QoL. In our study, all patients with typical AFl recurrence underwent a reablation procedure, except for one individual who underwent electrical cardioversion with no more AFl clinical episodes. DM is a chronic progressive disease associated with multiple complications, and so, by the time of follow-up, the disease has progressed and complications will have appeared; this would explain why the deterioration in QoL, both for physical and mental health, was more pronounced in these patients compared to those who do not suffer from DM. It is well known that the presence of AF is associated with impaired QoL, which significantly improves when a good heart rate control or sinus rhythm is achieved. OAC is very likely to be a risk indicator in patients who receive it, indicating that it is used in patients with more comorbidities and therefore at high risk of complications and impaired QoL. In addition, the numerous controls used to optimize the dose of anticoagulant therapy in patients with restricted mobility and who live far from health centers, such as it occurs in our study population, could contribute to a loss of QoL.So, patients that have undergone AFl ablation constituted a population presenting comorbidities that probably influenced the deterioration of QoL at baseline and at long-term follow-up. Nevertheless, ablation provided a significant improvement, chiefly for Physical Role, Vitality and Mental Health, and patients were able to perceive this improvement for Physical Role.Finally, the questionnaire completion rate was excellent; all patients answered the questionnaire at baseline (prior to ablation procedure) and at follow-up. Therefore, there were neither blank questionnaires nor incomplete items, unlike other studies ,24,25 inThis study was developed in a single hospital in Spain, so the interpretation of the results should be made with caution. More studies are needed to replicate these findings.The SF-36 is a generic questionnaire that evaluates most of the health-related areas relevant to multiple diseases and their treatment but, as a generic questionnaire, it is not designed to assess specifically QoL related to the treatment of arrhythmias. Furthermore, there are some important health aspects that are not covered in this questionnaire, such as sleep disorders, eating disorders, familial function, sexual function or cognitive function. In addition, both the ceiling and floor effect were observed for some dimensions, probably indicating that the SF-36 is not quite sensitive and specific enough to detect changes in these dimensions after the ablation procedure.CTI ablation of typical AFl provided a significant improvement in Physical Role, Mental Health and Vitality dimensions in a long-term follow-up, but MID was only observed for Physical Role. The main determinants of long-term QoL in these patients were baseline QoL, recurrence of AFl and a history of DM, AF and OAC.AF: Atrial fibrillation; Afl: Atrial flutter; CTI: Cavotricuspid isthmus; DM: Diabetes mellitus; ES: Effect Size; MID: Minimal important differences; OAC: Oral anticoagulation; QoL: Quality of life; SRM: Standardized response mean.The authors declare that they have no competing interests.PC and JG were responsible for the conceptuation and design of the study, performing electrophysiological procedures, acquisition of data, draft and revision of the manuscript. PC was also involved in acquisition of data, consent inform and Ethical Committee relationships and clinical follow-up. FG: participated in design, statistical analyses and interpretation of data and in manuscript revision, JLM and XF performed electrophysiological procedures and clinical follow-up. Finally JGJ gave the final approval of the version to be published. All authors read and approved the final manuscript.


This study assessed the influence of burnout dimensions and sleep difficulties on the quality of life among preclinical-phase medical school students. Data were collected from 193 students through their completion of the World Health Organization Quality of Life Instrument, the Maslach Burnout Inventory—Student Survey, the Mini-Sleep Questionnaire, the Social Readjustment Rating Scale, and the Beck Depression Inventory. This survey performed hierarchical multiple regressions to quantify the effects of emotional exhaustion, cynicism, academic efficacy, and sleep difficulties on the physical, psychological, social, and environmental components of an individual’s quality of life. The influence of confounding variables, such as gender, stress load, and depressive symptoms, were controlled in the statistical analyses. Physical health decreased when emotional exhaustion and sleep difficulties increased. Psychological well-being also decreased when cynicism and sleep difficulties increased. Burnout and sleep difficulties together explained 22 and 21 % of the variance in the physical and psychological well-being, respectively. On the other hand, physical health, psychological well-being, and social relationships increased when the sense of academic efficacy increased. Physical and psychological well-being are negatively associated with emotional exhaustion, cynicism, and sleep difficulties in students in the early phase of medical school. To improve the quality of life of these students, a significant effort should be directed towards burnout and sleep difficulties. Quality of life is a subjective state of well-being, which can be influenced by culture, value systems, and stressful environments . After about 30 days into the semester, we invited second-year medical students to complete self-administered questionnaires at the end of a lecture. The data sample was obtained from three different classes during three consecutive semesters. Students participated voluntarily, and did not receive any incentive. This study was approved by the local research ethics committee and all participants signed informed consent forms for the research study.The standardized self-report questionnaires were the short version of World Health Organization Quality of Life Instrument, the Maslach Burnout Inventory—Student Survey, the Mini-Sleep Questionnaire, the Social Readjustment Rating Scale, and the Beck Depression Inventory.The World Health Organization Quality of Life Instrument (WHOQOL-BREF) is a self-assessment questionnaire which measures individual perception of quality of life in the last 2 weeks (The WHOQOL Group The Maslach Burnout Inventory—Student Survey (MBI-SS) is an adapted version of the Maslach Burnout Inventory—General Survey (MBI-GS) that has been used among students in many countries  is a self-report of current sleep quality, which is measured by ten questions about the frequency of sleep difficulties. Answer options range from 1 (never) to 7 , with higher scores meaning more sleep difficulties. The total MSQ score is classified into good sleep (10–24), mild sleep difficulties (25–27), moderate difficulties (28–30), and severe difficulties (>30). The MSQ presents good internal consistency and a good reliability in the test–retest analysis. In undergraduate students, the Cronbach’s alpha was 0.77 and Pearson’s R ranged from 0.72 to 0.92, with exception one item (R = 0.55)  covers 43 life events with potential stress loads. Notable events are changes in family, occupation, economics, residence, affective, and social relationships in the last 12 months. When the event’s presence is checked, it receives a specific score. The scores of checked items are summed and classified as being low (≤149), mild (150–199), moderate (200–299), and major (≥300) (Holmes and Rahe The Beck Depression Inventory (BDI) assesses depressive symptoms in the last week. This scale comprises 21 self-report items and these responses are scored on a 0–3 scale describing severity levels . Preclinical medical students had a mean age of 21.42 (SD = 2.41).Considering the controlled covariates, women predominated slightly  in the survey sample. Moreover, this sample from the 193 respondents presented a mild/moderate level of depressive symptoms  and a moderate load of stress with life events . Specifically, 70 % (137/193) of the students reported minimal or mild/moderate depressive symptoms and 79.3 % (153/193) reported low, mild, or moderate stress with life events ; in the psychological domain, the mean score was 62.36 (SD = 16.01); in the social relationships domain, the mean score was 66.97 (SD = 20.51); and in the environment domain, the mean score was 61.97 (SD = 13.86). Compared to the general population , the score of physical health (WHOQOL-BREF) decreased by 3.7 points when the other variables are constant. Similarly, for one unit increase in MSQ score, physical health (WHOQOL-BREF) decreased by 0.6 units. In the psychological domain, the students had a poorer quality of life as cynicism and sleep difficulties increased. An increase in cynicism (MBI-SS) and MSQ scores of one unit was associated with a decrease in the psychological domain (WHOQOL-BREF) of 2.3 units and 0.4 units, respectively.On the other hand, the academic efficacy subscale had a protective role. The more the sense of academic efficacy increased, the more the psychological well-being increased. One unit increase in academic efficacy (MBI-SS) was associated with an increase in the psychological domain (WHOQOL-BREF) of 2.8 units. Similarly, a greater sense of academic accomplishment correlated with better physical health and social relationships. One point increase in academic efficacy (MBI-SS) was associated with 2.5 and 4.1 points increase in physical health and social relationships (WHOQOL-BREF), respectively.2 = 0.22, F = 23.04, p < 0.001] and psychological  domains of quality of life. Moreover, burnout dimensions and sleep difficulties also explained 9 %, and 6 % of the variance in the social  and environment  domains.The burnout and sleep difficulties model was relevant in explaining quality of life findings after controlling for the effects of gender, stress load, and depressive symptoms. The physical and psychological domains were the most affected by burnout and sleep difficulties. Combining burnout dimensions and sleep difficulties explained 22 and 21 %, respectively, of the variance in the physical [RConsidering the covariates, gender and depressive symptoms were associated with quality of life. The male students presented better physical health than females. As expected, the increase of depressive symptoms was related to the worsening of psychological, social, and environmental domains Table .Burnout dimensions and sleep difficulties were related to a decrease of psychological well-being and physical health among preclinical medical students. In the physical health domain, the students scored worse when emotional exhaustion and sleep difficulties increased. In the psychological domain, the score decrease was associated with the score increase in the cynicism and sleep difficulties. On the contrary, the psychological well-being, physical health, and the social relationships were better when the sense of academic efficacy increased.The quality of life in medical students is considered to be affected by burnout and sleep difficulties; however, the quantitative impact is unknown. Studies have addressed the relationship between burnout and sleep (Mazurkiewicz et al. Quality of life is directly linked to health care. Although medical students learn how to promote health care in patients they sometimes neglect their own health care. In this incongruous situation, medical students may associate health care with the weakness of a sick person, weaknesses which they deny as being relevant to their own physical and mental well-being. In addition, some medical academic learning environments can promote feelings of omnipotence in which future doctors feel that they have to be able to endure extreme academic demands and distressing situations. Thus, these distressing situations can promote sleep difficulties, cynicism, emotional exhaustion, and, consequently, a low quality of life in medical students.In the medical students surveyed, the decrease in physical well-being was connected with emotional exhaustion and low sleep quality. The physical domain of the WHOQOL-BREF includes activities of daily life and work capacity, which depend on the restorative functions of the body. These functions are affected by emotional exhaustion, which in turn reduces one’s energy and engagement with academic demands. Moreover, the sleep difficulties affect the vitality for everyday work and intensify sensitivity to the stressful experiences of medical learning (Vandekerckhove and Cluydts In our study, psychological well-being related negatively to cynicism and sleep difficulties. Students with detached attitudes toward medical learning are less likely to maintain altruistic and positive attitudes regarding social responsibility (Dyrbye et al. On the other hand, in our survey psychological well-being, physical health, and social relationships related positively to the sense of academic efficacy. The students’ sense of academic efficacy may affect self-esteem, positive feelings, personal health, and learning ability. More confident students can express their knowledge and doubts because they are involved with the learning process. Consequently, they interact better with peers and professors. Nevertheless, a mutual positive reinforcement may occur between academic efficacy and quality of life. Medical students with better psychological and physical health can better handle the problems they face in the academic learning.Educators and academic leaders have traditionally limited their role to academic teaching, and do not consider the effects of the learning environment on the physical and psychological well-being. Our study highlights the impact of medical school on quality of life through two negative effects, that is, burnout and sleep difficulties. Thus, our study suggests that educators and academic leaders should encourage stress management programs and sleep education in order to improve quality of life among students in the early phase of medical school.A disadvantage regarding the study’s methodology was that the data were collected at three different times in a cross-sectional manner. Furthermore, although this study controlled for the effects of some moderator variables, there may be other mediator and moderator variables that affected our results. Thus, future work should focus on identifying the long-term effects of burnout and sleep difficulties on the quality of life among medical students and doctors. Moreover, other confounders, such as cognitive abilities and personality traits, should be explored to clarify their role.Our results highlight the influence of burnout and sleep difficulties on the quality of life among preclinical medical students. In this study, physical health and psychological well-being were found to be affected by burnout and sleep difficulties. Thus, in order to improve quality of life in the early phase of medical school students, strategies need to be created to manage stress within the learning environment, to inform students of the importance of adequate sleep, and to strengthen academic efficacy.


This study evaluates the antihypertensive effect of long-term intake of a soluble cocoa fiber product (SCFP). Different doses of SCFP were evaluated  and a dose of 800 mg/kg/day of beta-glucan 0.75 (BETA-G) was used as a standard fiber. Water, a neutral vehicle, was used as negative control, and 50 mg/kg/day captopril was used as positive control. Systolic blood pressure (SBP) was measured weekly by the tail cuff method. Body weight, food, and liquid intake were also registered weekly in the rats from 10 to 24 weeks of life. Glucose, total cholesterol, and triglyceride levels; redox status; and the angiotensin-converting enzyme activity were also studied in the plasma samples of these animals.p<0.05; n=8). Paradoxically, neither the highest dose (800 mg/kg/day) of SCFP decreased SBP nor 800 mg/kg/day BETA-G . When the corresponding antihypertensive treatment, was disrupted the SBP values of the 400 mg/kg/day SCFP treated animals returned to control values . In addition, the SCFP significantly decreased  the glucose, cholesterol, and triglyceride levels and also the liver and plasma malondaldehyde levels. Moreover, the SCFP slightly increased the reduced glutathione levels in the liver.Throughout the 10 weeks of treatment, captopril and SCFP (400 mg/kg/day) demonstrated blood pressure lowering effects in the spontaneously hypertensive rats (The SCFP could be used to control the blood pressure of hypertensive subjects for a long period of time and could improve metabolic complications associated to cardiovascular diseases. Some food compounds may exert biological activities, and nowadays there is a growing interest on functional foods that could control arterial blood pressure. Functional foods are foods that show healthy properties besides their nutritional value. In particular, the close relationship between the consumption of foods rich in antioxidants and the drop of arterial blood pressure has assumed great importance in recent times, emerging as a non-pharmacological antihypertensive strategy , 2.Dietary fiber includes a group of food components, present in cereals, fruits, and vegetables, which are resistant to digestive enzymes. Attending to its water solubility, fiber can be classified into insoluble and soluble fiber . DietaryRecent research has been focused on cocoa and its products because of their antihypertensive properties that can be attributed to their high antioxidant polyphenol content , 11. DatThe chemical composition, polyphenol content, and antioxidant capacity of SCFP were characterized by Ramos et al. . Table 1ad libitum intake. Throughout the experimental period, the SHR of the established groups were fed a standard diet . From the 10th week of life until the animals were 20 weeks old (treatment period), the consumption of drinking fluids in these groups was as follows: tap water , 200 mg/kg/day SCFP, 400 mg/kg/day SCFP, 800 mg/kg/day SCFP, 800 mg/kg/day beta-glucan 0.75 (BETA-G) (fiber reference group), and 50 mg/kg/day captopril (positive control group). From 20 to 24 weeks of life (follow-up period), all groups consumed tap water as a drinking fluid. Weekly body weight of all animals was recorded up to the 24th week of life. Daily intake of drinking fluids and freely accessible feed was also estimated weekly in the animals from the different groups throughout the experimental period. Four 20-week-old rats of each group were killed by decapitation. Blood and liver samples were quickly collected from these animals for future analytical evaluations. Glucose, total cholesterol, triglyceride, and malondialdehyde (MDA) levels were determined in the plasma samples. These samples were also used to establish the plasma antioxidant capacity and the plasma ACE activity of the SHR. Subsequently, MDA and reduced glutathione (GSH) concentrations were also measured in liver samples.Forty-eight 10-week-old male SHR, weighing 255–265 g, were purchased from Charles River Laboratories (Barcelona-Spain) for this study. These animals were caged in groups of four rats, at a temperature of 23°C, with 12 h light/dark cycles. They were in turn randomly divided into six groups of eight animals with At the end of the experimental period, the 24-week-old rats were killed by decapitation, and the same tests and procedures recorded for the killed 20-week-old rats were applied to these animals as well.The experiments were designed and performed in accordance with the European and Spanish legislation on care and use of experimental animals  and were approved by the Ethics Committee at the Universidad Complutense de Madrid.The systolic blood pressure (SBP) was measured weekly in the SHR by the tail cuff method with some modification as described in Miguel et al. , during g for 20 min to obtain the plasma. A piece of liver tissue was homogenized at 4°C in a potter with phosphate-buffered saline (PBS) . The homogenates of liver were centrifuged at 5,000g for 15 min at 4°C, and the supernatant was recovered. Plasma samples and supernatants of liver samples were stored at −80°C until the analysis. Protein content in the liver samples was determined by the spectrophotometric technique . We used bovine serum albumin as standard .The blood samples were collected in tubes containing lithium heparin as anticoagulant and centrifuged at 3,500Glucose, total cholesterol, and the triglyceride levels in the plasma of the animals were determined using colorimetric assays from Spinreact , according to the manufacturer instructions. The plasma values were expressed as mg/dL.The antioxidant capacity of the plasma samples was determined using the oxygen radical absorbance capacity-fluorescein (ORAC) assay, previously described by Manso et al. . The fing for 15 min before adding TBA  to the supernatant in a proportion of 1:5 (v/v); then, the mixture was boiled at 97°C for 30 min. Spectrophotometric measurements at 535 nm were made at 20°C. The plasma MDA values were expressed as nmol MDA/ml plasma, and the liver MDA values were expressed as nmol MDA/mg tissue protein.Plasma and liver MDA values were measured by a thiobarbituric acid (TBA) assay, previously described by Rodríguez-Martínez and Ruiz-Torres  and modiS-transfer (1 U/ml) obtained from equine liver and monochlorobimane (1 mM) . The samples were then allowed to incubate in dark at room temperature for 30 min. The GSH–mCB adduct was measured using a Labsystems Fluoroskan II microtiter reader with excitation at 380 nm and the emission was measured at 470 nm. The liver GSH levels were expressed as µmol GSH/µg tissue protein.The reduced glutathione (GSH) levels in the liver were determined using the monochlorobimane (mCB) method described by Kamencic et al. . The fino-phthaldialdehyde in methanol. Fluorescence measurements were carried out at 37°C in a Fluostar Optima plate reader  with 350-nm excitation and 520-nm emission filters. The fluorescent plate reader was controlled by the Fluostar Optima software. Black 96-well polystyrene microplates  were used. A calibration curve with ACE from rabbit lung  was included in each plate. The ACE activity was expressed as mU ACE/ml plasma.The ACE activity in the plasma samples was measured by a fluorimetric method as explained by Miguel et al. .Then, trThe results are expressed as mean values±standard error of the mean (SEM) for a minimum of four rats and were analyzed by a one- or two-way analysis of variance (ANOVA) and the differences between the groups were assessed by the Bonferroni test and Student t test, using the GraphPad Prism software. We considered as the treatment period the time elapsed from the 10th until the 20th week of life and we considered the follow-up period from the 20th to the 24th week of life. Differences between the means were considered to be significant when the p values were <0.05.The SBP of the different groups of SHR are shown in p<0.05). When these treatments were disrupted, a reduction in the fluid intake was observed in the rats; however the animals that had been treated with 800 mg/day BETA-G maintained a drinking behavior slightly more pronounced than those of the other groups until the end of the experimental period (data not shown).Body weight increased progressively in all groups of rats from the beginning of the study, and throughout the experimental period, the growth was quite similar in the SHR treated with SCFP or BETA-G and in the negative control rats. However, from the 15th weeks of life, the body weight in the captopril group was slightly lower than in the remaining groups (data not shown). Food intake was also very similar in all groups along the experimental period (data not shown), but some differences could be observed in the fluid intake, even if it usually varied in all animals. In this context, we can stand out that the fluid intake in the SHR treated with 50 mg/kg/day captopril or 800 mg/day BETA-G was higher than that in the other rats (Plasma glucose was lower in the SHR that had been treated with 400 mg/kg/day SCFP or 800 mg/kg/day BETA-G than in the SHR that consumed tap water (negative control group). The animals treated with the remaining doses of SCFP also showed a slight decrease in glycaemia when compared with the negative control group, but no significant differences were appreciated in these comparisons. In addition, plasma glucose in the SHR treated with 50 mg/kg/day captopril was similar to plasma glucose in the negative control group. After the follow-up period, the glycaemia differences mentioned above could not be observed. Nevertheless, plasma glucose significantly increased in the animals that had been treated with 400 mg/kg/day SCFP when the treatment was disrupted .Total plasma cholesterol and plasma triglycerides were also lower in the SHR that had been treated with 400 mg/kg/day SCFP or 800 mg/kg/day BETA-G, than in the group that consumed tap water (negative control group). No differences were observed in these parameters in the SHR that had received the remaining treatments and the rats that were not treated. In accordance with glucose results, total cholesterol and triglycerides in the plasma significantly increased in the animals that had been treated with 400 mg/kg/day SCFP or 800 mg/kg/day BETA-G when the treatment finished  and 4.No differences were observed in plasma ORAC values and in liver reduced glutathione levels in the rats, neither at the end of the treatment period (20th week of life) nor at the end of the follow-up period (24th week of life) (data not shown). However, plasma MDA levels were lower in the SHR that had been treated with 400 mg/kg/day SCFP or 800 mg/kg/day SCFP, than in the SHR that consumed tap water (negative control group). Nevertheless, the plasma MDA levels in the SHR treated with 50 mg/kg/day captopril, 200 mg/kg/day SCFP or 800 mg/kg/day BETA-G, showed no significant differences when compared with the negative control group. When the corresponding treatments were disrupted, the plasma MDA levels of the groups that had been treated with 400 mg/kg/day SCFP or 800 mg/kg/day SCFP increased, and, at the 24th week of life, this biomarker was similar in all the animals a. Liver The ACE activity was significantly higher in the plasma of the SHR that had been treated with 50 mg/kg/day captopril than in the control group, but the plasma activity of this enzyme decreased in the captopril group when this treatment was disrupted. In fact, the plasma ACE activity of the rats that had been treated with captopril was similar to the corresponding values in the control rats at the end of the follow-up period. A slight, but not significant, increase of the plasma ACE activity was also observed in the rats treated with 800 mg/kg/day SCFP or 800 mg/kg/day BETA-G, and the animals of these groups showed also a decrease in the plasma activity of this enzyme when these treatments finished (data not shown).Fiber components organize functions of the large intestine and have important physiological effects on glucose, lipid metabolism, and mineral bioavailability . HoweverThe development of hypertension in SHR is very similar to that in humans  and, nowAs We should discard in any case that other possible compounds of SCFP that differ from polyphenols could be implicated in the antihypertensive effect of this fiber product. It is known that cocoa products are also rich in minerals, such as magnesium, potassium, and calcium, which have antihypertensive properties , 11, 31,When captopril and SCFP treatments were disrupted, arterial blood pressure rose gradually in the rats. This confirms the antihypertensive properties of these treatments. In fact, at the end of the follow-up period, the SBP values were similar in all groups of the SHR. Having in mind the marked effect of captopril, it was not surprising to observe that the reversion of the antihypertensive effect was slower in the group that had received this drug than in the group that had been treated with the SCFP.The SHR treated with captopril gained weight at a lower rate than did other animals, and these findings agree with previous studies showing that blockade of ACE system slows body weight gain in this rat strain .We have observed that food intake was similar in all animal groups. Nevertheless, liquid intake increased markedly in the rats that had ingested the captopril solution. This is not surprising because it has been demonstrated that ACE inhibitors induce thirst and increase water intake and urine output in rats . The aniAccording to the European Food Safety Agency, beta-glucan from any cereal maintains lower cholesterol levels and decreases plasma glucose levels . For theIt is well known that antioxidant therapy has positive results on hypertensive patients , 40. Thein vitro (ACE is critical for blood pressure control, and specific inhibitors of this enzyme are used as antihypertensive drugs. Polyphenols can inhibit this enzyme in vitro , 42. To in vitro –45 and ain vitro . A slighIn conclusion, long-term intake of SCFP improves SBP, glycaemia, and lipid profile in SHR. The SCFP also decrease lipid peroxidation in these animals. All these effects could indirectly promote a decrease in arterial blood pressure, but we should not forget that this fiber product contains polyphenols, and that these agents have demonstrated antioxidant properties and antihypertensive effect. Therefore, fiber products could benefit hypertension and related metabolic diseases, and the SCFP could in particular benefit this pathology. This study supports polyphenols are that responsible, at least in part, for the SCFP antihypertensive effect, and suggest, after appropriate clinical trials, to consider this product as a possible functional food ingredient for hypertensive patients.


Objective. More and more evidences demonstrate that androgen receptor (AR), epidermal growth factor receptor (EGFR), and breast cancer susceptibility gene 1 (BRCA1) have unique clinical implications for targeted therapy or prognosis in triple-negative breast cancer (TNBC). Therefore, we conducted a meta-analysis to summarize the possible associations. Methods. We retrieved published articles about AR, EGFR, and BRCA1 in TNBC from PubMed and EMBASE. The analysis was performed with Rev-Man 5.2 software. Results. A total of 38 articles were eligible for the meta-analysis. Our study showed that the expression level of EGFR  and the prevalence of BRCA1 mutation  were higher in TNBC than non-TNBC. In contrast, the expression level of AR was lower in TNBC than non-TNBC . In the subgroup related to EGFR expression, the level of EGFR expression was significantly increased in Asians (OR = 9.60) compared with Caucasians (OR = 5.53) for TNBC patients. Additionally, the prevalence of BRCA1 mutation in Asians  was higher than that in Caucasians . Conclusions. The distinct expression of AR and EGFR and the prevalence of BRCA1 mutation indicated that AR, EGFR, and BRCA1 might be unique biomarkers for targeted therapy and prognosis in TNBC. As one of the most common malignant tumors in female patients worldwide, breast cancer is recognized as a heterogeneous cancer, which shows substantial diversities related to biological behavior, therapeutic response, and clinical outcome . Gene exAs a subtype of breast cancer, TNBC is also a highly diverse group of cancers with unique molecular subtypes, which have distinct clinicopathologic characteristics and react dissimilarly to targeted agents and chemotherapy. By analyzing gene expression profiles, Lehmann et al.  identifiCompared with ER or PR in breast cancers, few researches are conducted for the roles of androgen and androgen receptor (AR) in breast cancers. AR, a member of the steroid hormone receptor family, is reported to be expressed in more than 70% of breast cancer , 10 and In general, not all TNBCs have a basal-like phenotype and not all basal-like breast cancers are TNBCs , but TNBThe cancer suppressor gene BRCA1 is involved in the process of DNA damage repair, recombination, cell cycle, and transcription . IntriguIt is the interest of studies for AR expression, EGFR expression, and BRCA1 mutation in TNBC patients, which offer help for treatment options or prognosis for TNBCs. Although the three biomarkers have been intensively studied, most of the research studied them, respectively, and the research results were not fully consistent. Thus, we performed a meta-analysis to systematically evaluate AR expression, EGFR expression, and the risk of BRCA1 mutation in TNBC.We collected literature by searching PubMed and EMBASE, with a combination of the following keywords: “AR and triple-negative breast cancer,” “EGFR and triple-negative breast cancer,” and “BRCA1 mutation and triple-negative breast cancer,” respectively, up to May 2014. We evaluated potentially relevant literature by scanning their titles and abstracts, or even full texts in the condition of having no idea about eligibility for publications. In addition, we paid an attention to the references of the qualified articles to see if there were more eligible ones.Candidate studies included in the meta-analysis had to satisfy all the following criteria: related to AR or EGFR or BRCA1 in TNBC; use a case-control design; sufficient published data for estimating an odds ratio (OR) or risk ratio (RR) with 95% confidence interval (CI); being limited to human subjects.The following criteria were used to exclude published studies: reviews and letters; lack of key information  for calculating OR for the expression of AR and EGFR or RR for the risk of BRCA1 mutation and 95% CI; non-English articles.For each of the eligible articles, the following data was extracted independently by two researchers (Zhang and Fang): first author's surname, year of publication, study origin, study objects, measuring method, positive judgement standards, and so on Tables , and 3.Z-test, and P < 0.05 was considered as statistically significant. Pooled OR or RR was carried out with Review Manager 5.2 software recommended by Cochrane Collaboration. In this meta-analysis, we define the exposed group as triple-negative breast cancer (TNBC) and nonexposed group as non-triple-negative breast cancer (non-TNBC). There are three parts in our analysis: one is for AR expression and TNBC; one is for EGFR expression and TNBC; and the last is for having the risk of BRCA1 mutation in TNBC.Crude ORs with their 95% CI were used to assess the strength of association between the expression of AR and TNBC and EGFR expression and TNBC, respectively. The same was RR and 95% CI for the risk of BRCA1 mutation in TNBC. The significance of the pooled OR or RR was determined by the Q-statistic was applied to investigate heterogeneity among studies with Review Manager 5.2 software. P value greater than 0.1 for Q-test indicated the absence of heterogeneity, and the fixed-effect model (Mantel-Haenszel method) was used to calculate pooled ORs. Otherwise, heterogeneity was present and the random-effect model (DerSimonian-Laird method) was more appropriate. In addition, the I2-test put forward by Higgins and Thompson was employed to accurately measure the degree of heterogeneity [I2 ranges from 0% to 100%, and I2 = 0~25% implied no heterogeneity, I2 = 25~50% moderate heterogeneity, I2 = 50~75% large heterogeneity, and I2 = 75~100% extreme heterogeneity [Heterogeneity in meta-analysis is concerned with the variation in research outcomes among different literature. The ogeneity . The valogeneity . PublicaWe retrieved the published literature about AR, EGFR, and BRCA1 in TNBC from PubMed and EMBASE. After being manually filtered in accordance with the inclusion and exclusion criteria, a total of 14 studies , 22–32 iThe main results of this meta-analysis were showed in Figures P < 0.00001), which we could see in P < 0.00001, I2 = 79%). In the stratified analysis by ethnic groups, the result showed that AR expression was slightly increased in Asians (OR = 0.11) compared with Caucasians (OR = 0.06) and the details were shown in For AR, significantly low expression was observed in TNBC , and there was statistical significance  among studies, so that a random-effect model was applied to calculate a pooled OR . As shown in P < 0.00001). Because of the extreme heterogeneity, we did a subgroup analysis according to the antibody source and the result was shown in The analysis of EGFR expression in TNBC was performed and it showed extreme heterogeneity . It indicated that women with TNBC were approximately five times more likely to have BRCA1 mutation compared with non-TNBC and it was statistically significant (P < 0.00001). In the subgroup with regard to ethnicity, the pooled RR  for the Asians was higher than the pooled RR  for the Caucasians, which indicated that the prevalence of BRCA1 mutation was higher in the Asians compared with the Caucasians  and EGFR expression . The detection methods of AR and EGFR are both immunohistochemistry (IHC), but the antibody source, dilution rate, cut-off value, and ethnicity are different for AR and EGFR in different studies , but more and more studies demonstrated that about one-third of TNBCs were AR-positive , 29, 30.In the recent years, more studies have been carried out for the association between EGFR and various kinds of cancers. And the results were nearly consistent with our meta-analysis which showed that the EGFR expression was upregulated in TNBCs compared with non-TNBCs . Based on the EGFR overexpression in TNBCs, numerous trials have been currently focusing on identifying possible therapeutic targets and prognosis for the TNBC patients with EGFR overexpression. Although the TNBC cell lines were not essentially sensitive to the EGFR inhibitor , gefitinib could improve response to chemotherapy. That was to say combination therapy with gefitinib and chemotherapy made a greater difference to inhibit proliferation of TNBC cells than either gefitinib or the chemotherapy alone  indicateI2 = 0%, P = 0.71) in the Asian subgroup. Thus, the race was in a certain contribution to the heterogeneity and a factor causing the different prevalence of BRCA1 mutation between Caucasoid and Asian. Several studies had been conducted for the relationship related to the BRCA1-associated breast cancers and therapeutic effects. Byrski et al. [The prevalence of BRCA1 mutation in familial or early-onset breast cancer led more and more studies to concentrate on the role of BRCA1 in TNBC , 46, 49.i et al.  reportedi et al. . HoweverIn addition, some research studies have been carried out for other therapeutic target receptors  and novel inhibitors  for the preclinical and clinical treatment of TNBC. Similar to EGFR, the vascular endothelial growth factor receptor (VEGFR) has been explored as a therapeutic target receptor in breast cancer. An open-label, randomised phase 3 trial demonstrated that bevacizumab (VEGFR inhibitor) was ineffective in adjuvant treatment in unselected TNBC patients but may have some efficacy in metastatic TNBC . A recenBased on the gene expression profiling, triple-negative breast cancer is a heterogeneous disease with unique molecular subtypes which have different clinicopathological features and clinical outcomes. Taken collectively, AR, EGFR, and BRCA1 play distinct roles as biomarkers in the progression of TNBCs. In view of the EGFR overexpression and the immunohistochemical feasibility of clinical practice, EGFR might be superior to AR and BRCA1 as biomarker for TNBCs. However, the unique role of AR and BRCA1 cannot be ignored for targeted treatment strategies and prognosis judgement. Furthermore, the previous study reported that 20% of the hereditary BRCA-related breast cancers had triple-negative phenotype and expressed AR . To dateOverall, by quantifying synthesis of all published studies of AR, EGFR, and BRCA1, the meta-analysis demonstrated that the expression level of EGFR and the risk of BRCA1 mutation were higher in TNBC compared with non-TNBC and AR expression was downregulated. Our study can give a valuable clue for the targeted therapy or judging prognosis of TNBC patients. More clinical research should be performed before AR, EGFR, or BRCA1 can be proved to be common biomarkers for routine clinical practices.


Over the last 20 years in biotechnology, the production of recombinant proteins has been a crucial bioprocess in both biopharmaceutical and research arena in terms of human health, scientific impact and economic volume. Although logical strategies of genetic engineering have been established, protein overexpression is still an art. In particular, heterologous expression is often hindered by low level of production and frequent fail due to opaque reasons. The problem is accentuated because there is no generic solution available to enhance heterologous overexpression. For a given protein, the extent of its solubility can indicate the quality of its function. Over 30% of synthesized proteins are not soluble. In certain experimental circumstances, including temperature, expression host, etc., protein solubility is a feature eventually defined by its sequence. Until now, numerous methods based on machine learning are proposed to predict the solubility of protein merely from its amino acid sequence. In spite of the 20 years of research on the matter, no comprehensive review is available on the published methods.Escherichia coli recombinant protein overexpression system. The models are investigated and compared regarding the datasets used, features, feature selection methods, machine learning techniques and accuracy of prediction. A discussion on the models is provided at the end.This paper presents an extensive review of the existing models to predict protein solubility in This study aims to investigate extensively the machine learning based methods to predict recombinant protein solubility, so as to offer a general as well as a detailed understanding for researches in the field. Some of the models present acceptable prediction performances and convenient user interfaces. These models can be considered as valuable tools to predict recombinant protein overexpression results before performing real laboratory experiments, thus saving labour, time and cost. Escherichia coli (E. coli), a bacterium that requires simple conditions to grow is still the favoured host for cloning and overexpressing most proteins which are non-glycosylated and do not have many cysteine residues [In biotechnology, production of recombinant proteins is a crucial process in both biopharmaceutical industries and scientific research. So far, residues .Even though logical strategies of genetic engineering are well established, such as strong promoters and codon optimization, protein overexpression is often, still an art. In particular, heterologous expression is often afflicted with low levels of production and insoluble recombinant proteins forming inclusion bodies (protein aggregations). Yet, there is no generic solution available to enhance heterologous overexpression. The use of fusion proteins can sometimes be more successful at the expense of decreased total yield as a result of the fusion partner production. Features that differentiate between proteins in the negative (non-expressed) and positive (expressed) classes might indicate sequence characteristics that could be modified in optimization, corresponding to what was attained with codon optimization, where sequences of gene are modified to become compatible with the translational apparatus . As the For a given protein, the extent of its solubility can indicate the quality of its function. In general, over 30% of recombinant proteins are not soluble . About 3E. coli at the normal growth temperature of 37°C [The trial-and-error procedure of protein overexpression can be avoided by identifying the promising proteins to improve the experimental success rate . There a of 37°C .The correlation of amino acid sequence and the tendency to form inclusion body was shown for the first time by Wilkinson and Harrison . Later, Protein solubility prediction can be considered a binary classification task where a classifier should discriminate between soluble proteins (positive samples) and insoluble proteins (negative samples). There are several classification methods  namely, decision tree (DT) (e.g. C4.5 ), k-nearThe learning algorithm (i.e. the classification method) is selected based on numerous factors, such as the number of existing examples in the dataset, the data type to be classified (e.g. symbolic or numeric), and the number of examples probable to be inaccurate or noisy. The level of preferred interpretability of the outcomes is another issue to be considered .The majority of current methods use SVM to build the model of solubility . ApproprA. niger or the E. coli system. The works of Hirose et al. [E. coli and wheat germ).To date, all of the prediction approaches examined a single system of protein expression, such as the e et al. ,10 are eSome of the suggested methods of prediction offer their work as widely accessible web servers ,10,17-20In spite of more than two decades of research on the subject, there has been only one report, reviewing seven solubility prediction tools . In theiThe organization of the paper is as follows. The major protein solubility prediction studies are reviewed in section 2, with emphasis on their datasets, features, feature selection methods, predictor models and performance results. Section 3 presents a discussion on the models details, the best models and the data challenge for solubility prediction task. Lastly, section 4 concludes the paper and proposes some future research directions.. Due to space limitation, the reported performance of the works and the features used in each work are shown in Table The methods to predict solubility of protein based on the machine learning are summarized in Table In the following tables, for an entry which does not have the corresponding column value, symbol “-” is used. For an entry which we could not find its value, but may exist, symbol “N/A” is used .”In order to comprehend the details of the works which are presented in Table It should be mentioned that in some works several modeling techniques are examined and then one or more are selected as the final model(s). In the “Modeling Technique(s)” column of Table With respect to the data used in each study, some of the authors created a dataset harvested from the literature, some employed public datasets, while others performed experiments to generate their own dataset.This section investigates the works in more depth. In the following paragraph, the most used dataset, features, feature selection methods and learning techniques are presented. Afterwards, the best models based on the obtained accuracies are introduced. Then, the most convenient to use models are mentioned. Lastly, some data-related challenges are discussed.In terms of data, eSol is the most widely used dataset in the field. Considering input features, the following features are the most common ones computed from the protein sequence: aliphatic index, amino acid sequence length, charge, amino acid compositions, instability, isoelectric point (pI), hydrophilicity, molecular weight, and predicted secondary structure. Filter methods . Especially the ones with convenient user interfaces (e.g. web applications), can be considered valuable tools to anticipate recombinant protein overexpression results before performing real laboratory experiments. This capability will lead to significant reduction of labour, time and cost.E. coli and discovering other influential features, are some considerations for future directions in the protein solubility prediction field.Generating larger and more accurate datasets, working on organisms other than The authors declare that they have no competing interests.NH carried out the literature review studies and drafted the manuscript. SZMH and MRS conceived the idea of the study, and helped to draft the manuscript. AN helped to draft the manuscript. All authors read and approved the final manuscript.NH received her M.Sc. in Artificial Intelligence from Isfahan University of Technology, Iran, in 2009 and B.Sc. in Software Engineering from the same university, in 2005. She is a faculty member of the Islamic Azad University (IAU) in Iran, since 2011. Presently she is pursuing Ph.D. in Computer Science at Universiti Teknologi Malaysia. Her research interests are bioinformatics, synthetic biology, artificial intelligence and machine learning.SZMH is an Associate Professor at the Department of Software Engineering, Faculty of Computing, Universiti Teknologi Malaysia (UTM). She received her B.Sc. Degree in Computer Science from University of Harford, USA, M.Sc. in Computing from University of Bradford, UK and Ph.D. research in Soft Computing from University of Sheffield, UK. Her research interests are Soft Computing techniques and applications, System Development and Intelligent System. Currently she is the Deputy Dean of Academic, Faculty of Computing, UTM and a member of Soft Computing Research Group (SCRG), K-Economy, UTM.AN received his M.Sc. in Computer Engineering from Islamic Azad University, Iran, in 2006 and B.Sc. in Computer Science from Yazd University, Iran, in 2003. He is a faculty member of the Islamic Azad University (IAU) in Iran, since 2007. Presently he is pursing Ph.D. in Computer Science at Universiti Teknologi Malaysia. His research interests focus on machine learning, pattern recognition and computer vision.MRS received his Ph.D. from University of New South Wales, Australia, in Biotechnology. He is currently a faculty member (Professor) in the School of Biological Sciences, Universiti Sains Malaysia. The research in his laboratory focuses on molecular genetics and structural biology of proteins. He has published extensively in these areas.In detailed descriptions of 24 studies to predict protein solubility during 1991–2014 (February).Click here for file


Exposure to particulate matter air pollution (PM) has been associated with cardiovascular diseases.In this study we evaluated whether annual exposure to ambient air pollution is associated with systemic inflammation, which is hypothesized to be an intermediate step to cardiovascular disease.x). In addition, traffic intensity on the closest street and traffic load within 100 m from home were used as indicators of traffic air pollution exposure.Six cohorts of adults from Central and Northern Europe were used in this cross-sectional study as part of the larger ESCAPE project (European Study of Cohorts for Air Pollution Effects). Data on levels of blood markers for systemic inflammation—high-sensitivity C-reactive protein (CRP) and fibrinogen—were available for 22,561 and 17,428 persons, respectively. Land use regression models were used to estimate cohort participants’ long-term exposure to various size fractions of PM, soot, and nitrogen oxides , but the effect estimate was more sensitive to model adjustments. For fibrinogen, no consistent associations were observed.Particulate air pollution was not associated with systemic inflammation. However, cohort participants living on a busy  road had elevated CRP values . Annual NOLiving close to busy traffic was associated with increased CRP concentrations, a known risk factor for cardiovascular diseases. However, it remains unclear which specific air pollutants are responsible for the association.http://dx.doi.org/10.1289/ehp.1408224Lanki T, Hampel R, Tiittanen P, Andrich S, Beelen R, Brunekreef B, Dratva J, De Faire U, Fuks KB, Hoffmann B, Imboden M, Jousilahti P, Koenig W, Mahabadi AA, Künzli N, Pedersen NL, Penell J, Pershagen G, Probst-Hensch NM, Schaffner E, Schindler C, Sugiri D, Swart WJ, Tsai MY, Turunen AW, Weinmayr G, Wolf K, Yli-Tuomi T, Peters A. 2015. Air pollution from road traffic and systemic inflammation in adults: a cross-sectional analysis in the European ESCAPE project. Environ Health Perspect 123:785–791;  Exposure to ambient particulate matter pollution (PM) affects both respiratory and cardiovascular health, and is a major contributor to the global burden of disease . One of Ischemic heart disease is the leading contributor to the burden of disease worldwide, and stroke is ranked third . An AmerIt has been hypothesized that increased systemic inflammation—a risk factor for, as well as a consequence of, atherosclerosis—is the main underlying mechanism linking long-term PM exposure to incidence of CVD . A numbeStudy population. The ESCAPE project linked data from existing cohorts in different parts of Europe with modeled long-term residential air pollution concentrations. The studies were approved by the local ethical committees and conducted according to the guidelines laid down in the Declaration of Helsinki. All data were collected in accordance with the Declaration of Helsinki, and all participants gave an informed consent before the study. Data on blood levels of high-sensitivity CRP was available for five cohorts in Northern and Central Europe: the National FINRISK study in Finland, KORA  and HNR  in Germany, SAPALDIA (Swiss Study on Air Pollution and Lung and Heart Disease In Adults) in Switzerland, and TwinGene in Sweden. For the analyses of fibrinogen, four cohorts were available: FINRISK, KORA, HNR, and the “60-year-olds” study in Sweden. Descriptive statistics of these cohorts are presented in Exposure data. Air pollution measurements and modeling followed common study protocols , black carbon (PM2.5 absorbance), that is, soot, and nitrogen oxides (NO2 and NOx) were measured  at the road nearest to the participant’s residence, and traffic load on major roads within 100 m of the residence (measured as the product of traffic intensity and the length of major road fragments within a 100-m buffer). Databases on traffic intensity were constructed for each cohort based on measurements conducted by county- or municipal-level authorities . The traData analyses. One blood sample per person was available for the analyses, taken at the baseline visit except for SAPALDIA (first follow-up visit). High-sensitivity CRP and fibrinogen on continuous scales were used for the current cross-sectional analyses. Based on the distribution of inflammatory blood marker concentrations and model residuals, the  logarithmic value of CRP concentrations was used in the analyses, whereas fibrinogen concentrations were not transformed. Linear regression models in SAS (SAS Institute Inc.) and STATA (StataCorp) software were used for the analyses. In the meta-analyses, cohort-specific effects were treated as having a random component apart from sampling error, and pooled using the empirical Bayes method. Heterogeneity of the cohort-specific estimates was estimated using Cochrane’s Q test. Effect estimates are presented as percent difference from the outcome mean together with 95% confidence interval (CI), and are calculated for an increase of 5 μg/m3 in PM2.5 and PMcoarse, 10 μg/m3 in PM10 and NO2, 20 μg/m3 in NOx, and 1 × 10–5/m in PM2.5 absorbance. An association was deemed present when it was statistically significant (p < 0.05).a priori based on literature on the determinants of CRP and fibrinogen concentrations. Four different regression models were used to calculate the effect estimates. All these models included, in addition to exposure variables, an indicator variable for baseline visit for FINRISK and KORA, which had more than one recruitment period, and an area indicator for FINRISK, which consisted of two clearly separate study areas. Additional variables controlled for in the first regression model (the crude model) were age and sex. The second model (the main model) also included education , body mass index, smoking status , physical activity , and alcohol intake . Effect estimates were also calculated using an extended model, which included additional covariates not available in all cohorts .Confounders in the statistical models were selected The fourth model was a mixed model that included the same covariates as the main model, but also included neighborhood level as a random effect to take into account possible spatial clustering of observations. Depending on data availability for each cohort, neighborhoods either were defined as grids or were based on ZIP code areas. We assumed that the effect of neighborhood on health was mainly attributable to area level socioeconomic status. Therefore, area level median household income or unemployment rate were included in the model as fixed effects.2 for body mass index) and sex was evaluated by adding an interaction term in the main model. In addition, a number of sensitivity analyses were conducted using the main model: exclusion of participants with high (> 10 mg/L) CRP values that may indicate a current bacterial infection, exclusion of study participants who moved residence during the 2 years before blood draw , use of back-extrapolated concentrations of NOx, NO2, and PM10 (in cohorts where changes over time in concentrations had occurred), inclusion of indicators for medication use (statins and antihypertensives), and finally inclusion of traffic noise for a subset of data in each center . Traffic noise was modeled according to the guidelines of the EU noise directive  and traffic intensity at the nearest road  without evidence of significant heterogeneity between ESCAPE cohorts  , but significant for HNR  .In the pooled analyses using the main model, CRP serum levels were positively associated with annual NO cohorts . Categorp < 0.1) positive associations were observed for NOx and traffic load within 100 m (in the two highest categories) without evidence of heterogeneity , but nonsignificant for HNR  . Finally, the middle category of traffic intensity was positively associated with fibrinogen in the pooled analyses, but there was no evidence of association for the other categories.In the pooled analyses for fibrinogen, borderline significant .Estimated effects of air pollution or traffic were not modified by obesity or sex: The confidence intervals were overlapping in the pooled analyses, and no consistent patterns were observed in the cohort-specific analyses (data not shown). Inclusion of environmental noise in the main model for CRP increased effect estimates for traffic intensity in the two highest categories  . Inclusion of information on statin use in the model and exclusion of persons who had recently moved led to decreased estimated effects of NOcoarse .There were only minor changes in the effect estimates, when back-extrapolated air pollution levels were used in the models for CRP and fibrinogen (data not shown). In general, sensitivity analyses had only minor effects on the effect estimates for fibrinogen .After exclusion of unusually high CRP values , effect estimates increased for PMx, an indicator for vehicle exhaust, was also associated with CRP serum levels. However, the effect estimate was more sensitive to further adjustments in the model, such as inclusion of area-level confounders. Fibrinogen was not consistently associated with air pollution, and there was only limited support for a positive association with traffic exposure.In this European multi-center study, modeled annual particulate air pollution concentrations were not associated with systemic inflammation. However, high traffic intensity on the road nearest to home was associated with increased levels of high-sensitivity CRP, an established marker for systemic inflammation. In the main analyses, long-term exposure to NOx was the only pollutant that was positively associated with CRP in the analyses performed with the a priori–selected main model. However, the association between NOx and CRP was somewhat sensitive to adjustments in the models, such as inclusion of area-level confounders or information on statin use or moving history. Therefore, further studies are needed to confirm the suggestive association. Furthermore, it is possible that nitrogen oxides are not causally related to systemic inflammation, but that they rather represent markers for traffic-related air pollution mixture, including ultrafine particles, volatile organic compounds, and traffic-related PM2.5.CRP is an acute-phase reactant that has been shown in many cohort studies to be a reliable measure of underlying systemic inflammation and a predictor of future myocardial infarction and stroke . In the 2.5 absorbance, which is considered to be a key component of the near-road traffic-related pollution mixture. One reason for this might be that soot is stable in the atmosphere and is therefore associated not only with fresh but also with aged vehicle exhaust, which may be less toxic due to secondary atmospheric reactions. On the other hand, NOx is a better marker for vehicle exhausts than soot, which also has other (combustion) sources such as residential wood combustion  than of NOx (R2 = 86%) , transition metals (wear of brakes and clutch), and biological material . All these components have been shown in toxicological studies to have considerable proinflammatory potential . In the 2 = 86%) .2.5 or PM10, the spatial variation of which is less strongly associated with road traffic than that of NOx  of each postcode sector; the same exposure estimate was assigned to all study participants within the sector. The spatial resolution of exposure assessment was higher in the present study, which might explain the discrepancy concerning CRP. In a German study that used the HNR cohort and dispersion models, PM2.5 was found to be associated with CRP in men but not in women . In the same study, NO2 was also associated with another marker of systemic inflammation, interleukin-6. In a cross-sectional study conducted in a representative sample of adults ≥ 54 years of age in Taiwan  and lower variability in concentrations—both factors that reduce the chance of identifying associations.Fibrinogen is a hemostatic factor with proinflammatory properties. It has been shown that inflammatory and coagulatory processes are intertwined via many molecular mechanisms, and typically systemic inflammation is associated with increased levels of fibrinogen . One preThe most robust association in the present study was observed between traffic intensity at the road nearest to home and CRP. Cohort participants living on a busy road  had significantly increased CRP compared with participants living on a quiet residential street . The estimated increase was modest (10.2%), but can be seen as clinically significant considering that CVD risk seems to increase linearly with increasing CRP . It is nInhalation of particulate air pollution is known to cause pulmonary oxidative stress and pulmonary inflammation , which iMost of the evidence on the health effects of PM relates to cardiorespiratory health. However, some recent studies have associated long-term PM exposure with additional outcomes such as rheumatoid arthritis, diabetes, cognitive impairment, and leukemia . ImportaAs part of the large European ESCAPE project, this study has some major strengths, including the large number of observations, a multi-city study design covering many types of exposure environments and climates, rigorous exposure assessment including extensive quality control measures, and the use of common study manuals for exposure assessment, data management, and data analyses. An obvious limitation is the cross-sectional nature of the study. However, a large number of individual-level and some neighborhood-level covariates were available for inclusion in the statistical models to reduce confounding. It was unfortunate that data on individual-level income, a quantitative indicator of socioeconomic status, was not available. However, we believe that residual confounding by individual level socioeconomic status would have been substantially reduced by adjusting for educational level and lifestyle factors including smoking. The association between traffic intensity at the road nearest to home and CRP was not sensitive to model specifications, which increases the plausibility of our main finding.2.5 or coarse particles, the apparent lack of association for the latter could be attributable partly to the difficulty of predicting concentrations. Finally, there is evidence that living close to traffic contributes significantly to personal exposures  PDFClick here for additional data file.


A form based on the MSDH was used to collect sociodemographic dataaddressing individual, proximal, intermediate determinants and the influence ofsocial networks together with an instrument used to assess the QoL of people withHIV/AIDS. The project was approved by the Institutional Review Board (Protocol No.040.06.12).  according to MSDH, most men with AIDS were between 30 and 49 years old (68.1%),mixed race (59.4%), heterosexual (46.4%), single (64.5%), Catholic (68.8%), had abachelor's degree (39.2%), had no children (61.6%), and had a formal job (71.0%).The perception of QoL in the physical, level of independence, environment, andspirituality domains was intermediate, while QoL was perceived to be superior inthe domains of psychological and social relationship. A perception of lower QoLwas presented by homosexual (p=0.037) and married men (p=0.077), and those withincome below one times the minimum wage (p=0.042). A perception of greater QoL waspresented by those without a religion (p=0.005), living with a partner (p=0.049),and those who had a formal job (p=0.045).  social determinants influence the QoL of men with AIDS. The epidemic is currently stable in Brazil and concentrated in vulnerablepopulation groups, but male adults are still the most frequently affected(-).The Human Immunodeficiency Virus (HIV) infection is currently a health problem due toits pandemic nature and severity. A total of 686,478 cases of AIDS were reported to theNotifiable Diseases Information System (SINAN) from 1980 to December 2013; 445,197 ofwhich refer to men and 241,223 to women.The availability of antiretroviral treatment (ART) in Brazil since 1996 has enabled areduction in both morbidity and mortality caused by HIV. Brazil was the first developingcountry to adopt a public policy for patients to have access to ART and is recognizedworldwide for providing a program that has achieved good response against the HIV/AIDSepidemic..Even though there is a national program and very well-organized to combat sexuallytransmitted diseases (STD) and AIDS, one should consider that economic and politicalaspects have an essential meaning to each population in which AIDS has beendisseminated. Most cases of AIDS are located in poor countries, suggesting the need toanalyze the social determinants of health in these populations.Because ART has enabled increased survival rates of people with HIV/AIDS, characterizingit as a chronic disease, the health care provided to these individuals gains greaterimportance for these individuals who require unique care procedures to maintain theirquality of life (QoL) that has been already validated in Brazil. QoL is a perception of individuals in regard to their position in life inthe context of the culture and value system in which they live and in relation to theirobjectives, expectations, standards and concerns. Studies show that the QoL of people with HIV/AIDS is compromised due todiscrimination and the unfavorable socioeconomic conditions in which they live, whichmay determine increased rates of mortality(-).The World Health Organization (WHO) developed, within a multi-center collaborativestudy, an instrument to assess QoL from an international and cross-cultural perspective.This instrument is called the World Health Organization Quality of Life WHOQOL-100),which originated a specific instrument for people living with HIV/AIDS,WHOQOL-HIV that han Brazil. QoL isconcerns. Studieortality-10.0,which Given the previous discussion and with the intent to contribute to the quality ofhealthcare provided to people living with HIV/AIDS, considering that most individualsaffected by HIV infection are male and that social determinants impacting this process,we proposed this study to analyze the QoL of men with AIDS using the WHOQOL-HIV bref,with the Model of Social Determinants of Health (MSDH) as theoretical framework..The social determinants of health are the social conditions in which people live andthat affect people's health. There are different models of social determinants of healthbut the National Commission on the Social Determinants of Health chose Dahlgren andWhitehead's model to be used in Brazil due to its simplicity and clear graphicrepresentation of social determinants., the social determinants of health are displayed in concentric layers,where individuals are in the center of the model: layer 1 ; layer 2 ; layer 3 ; layer 4 ; layer 5 .In this model, the soThis cross-sectional study with quantitative approach was conducted in an infectiousdisease outpatient clinic in a Brazilian university hospital that provides care toadults with HIV/AIDS. This hospital has an outpatient service, inpatient wards and anintensive care unit and also provides laboratorial and radiological exams, ART andcondoms., with a 95% confidence level that the estimation error would not surpass3%, considering that the mean of these scores, according to prior studies(-), is about 13.7, with a standard error of 3.8, and also that there were 235male patients receiving care from the outpatient clinic up to the end of 2001. For that,the following expression was used:Data were collected over the course of one year. In order to meet the study'sobjectives, the sample size was determined to estimate the mean of the scores obtainedin the domains assessing the QoL of people living with HIV/AIDS, the WHOQOL-HIVbref, with a studies-14, iGC is equal to the z-statistic (1.96), standard deviation(SD), X̅ and ε correspond to mean and acceptable error (0.03), respectively. Hence, asample of 138 patients was computed.In this formula, zInclusion criteria were: being a man and having AIDS; being older than 28 years of age;being in outpatient follow-up; using ART; and signing a free and informed consent form.Exclusion criteria were having access to ART at the hospital but with follow-upperformed in a private facility; suffering from mental disease or any other conditionthat would impede the individual from answering the study's forms. The participants wereinvited to participate in the study when they attended the outpatient consultations. Twoforms were applied through interviews in a private room. (12) to address thesociodemographic characterization of people with HIV/AIDS and was arranged into fourlayers 1- identification, age, race; 2 - category of exposure, marital status, religion,schooling; 3 - number of children, number of household members, and whether theindividual lives with a partner; 4 - occupation and per capita income(times minimum wage). The form was based on the MSDH layers 1, 2, 3 and 4, while layer 5was used in the discussion of findings because it refers to the distal ormacro-determinants involving economic, cultural, and environmental conditions ofsociety, current policies, supranational determinants and globalization and does notdirectly refer to the personal characteristics of the study's participants. The form wasvalidated after being applied to 20 male individuals with AIDS, who did not compose partof the sample.A form was developed in accordance with MSDH. The full version includes 120 questions (WHOQOL-HIV), so the brief version(WHOQOL-HIV bref) was used instead. It assesses the generic QoL of people with HIV/AIDS.WHOQOL-HIV bref has 31 items measuring QoL distributed into six domains: I. Physical; II. Psychological ; III. Level ofIndependence ; IV. Social Relationships ; V. Environment ; VI.Spirituality/religion/personal beliefs . The questions are scored on a 5-point Likert scale containing 1 , 2 (a little), 3 (a moderate amount), 4 (very much) and 5 (an extreme amount),such that 1 indicates negative perceptions and 5 indicates positive perceptions. Thescores obtained in each domain are scaled in a positive direction, where higher scoresindicate better QoL. For the items pain, discomfort, negative feelings, dependence onmedication, death and dying, scores are not scaled in a positive direction and higherscores do not represent better QoL and need to be inverted. Scores range from 4 to 20points, which reflect worst and best QoL, respectively.The other form was an instrument used to assess the QoL of people with HIV/AIDS, theWorld Health Organization Quality of Life instrument - HIV/AIDS module (WHOQOL-HIV), thePortuguese version of which has already been validated in Brazil. The fuectively.(-).The classification of previous studies addressing people living with HIV/AIDS was usedto characterize the level of perception of QoL in each domain in which the scorestranslated, as follows: between 4 and 9.9 indicate a perception of low QoL, from 10 to14.9 indicate a perception of intermediate QoL, and scores from 15 to 20 represent aperception of superior QoL-14.(r) and processed by theStatistical Package for Social Sciences (SPSS) version 18(r). Absolute andrelative frequencies, mean, standard deviation, median, minimum and maximum values wereused in the descriptive statistics. Analysis of variance (ANOVA) was used to compare themeans of the WHOQOL-HIV bref's domains with the variables of interest and Tukey's testand the T test were also applied for the intragroup analyses. Level of significance wasestablished at 5% and considered statistically significant when p <0.05.Data were organized in Microsoft Excel 2007The study project was approved by the Institutional Review Board on July 30, 2012 inaccordance with Resolution No. 196/96, National Council of Health (Protocol No.040.06.12). The participants signed free and informed consent forms and anonymity wasensured; the study's data were used only for scientific purposes.per capita monthly income more than two times the minimumwage.Most men had no children (61.6%) and only 11.6% reported more than six children, withnine being the highest number of children reported. Most lived together with three tofive people (47.1%), had a formal job at the time of the study (71.0%), and 58.0%reported a The analysis of association between the scores of the WHOQOL-HIV bref's scores and theMSDH's layers 1 and 2 presented statistical significance in some situations. The meanscores of homosexual participants for the domain VI were lower than that of heterosexualmen, showing a perception of lower QoL concerning spirituality (p=0.037). Married menobtained lower scores in domain V (environment) in comparison to single men (p=0.077).Those who did not report a religion scored higher than the Catholic participants in thefollowing domains: I (p=0.005), II (p=0.017) and III (p=0.038) .per capita income below one times the minimum wage (p=0.003)and between one and two times the minimum wage (p=0.042) scored lower on average in thedomain when compared to individuals with per capita income greater thanthree times the minimum wage . Men with a formal job scored higheron average on domains II (p=0.045) and III (p=0.023) than those without formal jobs.Those with mum wage ..The social determinants of health are important because they predict the proportion ofvariation in one's health condition, sanitary inequity, and health-related behaviors.The social determination of health is rooted in an ethical foundation that is equity,defined as the absence of unfair differences among population groups so that inequitiesin health are socially-produced differences.. In regard to race, the results were similar to those found by a studyconducted in Maranhão, Brazil in which mixed race was prevalent. Note that individual determinants are, in general, considered to benon-modifiable determinants.According to MSDH's layer 1, which depicts individual determinants, the age of mostindividuals was between 30 and 49 years old, revealing national dynamics in which mostmen infected with AIDS between 2000 and 2011 were in this age rangerevalent. Note t. This finding involves the issue of vulnerability in regard to HIV/AIDS,which is linked to a set of individual and behavioral aspects that facilitate onebecoming infected, in addition to sociopolitical aspects, which are represented by thecommitment displayed by authorities, inter-sector actions and funding.The analysis of layer 2 showed that the category of exposure heterosexual waspredominant, which also represents the national context. This f funding.. In regard to education, most had a bachelor's degree and percapita income greater than two times the minimum wage, differing from thefindings of other studies, where most men with AIDS had low educational levels andincome, and performed occasional jobs without formal contracts. Most men had no children, which may be explained by the considerablenumber of homosexual (39.9%) and bisexual (13.7%) individuals.Most men with AIDS were single and Catholic, which also was observed in anotherstudy. In regtracts,,17. M(-). Note that the lowest scores are for domain III, which represents level ofindependence. Hence, the individuals face changes in their mobility, activities of dailyliving, depend on medication and treatment, in addition to experiencing interference intheir capacity to work. These results are related to changes in lifestyle after thediagnosis of HIV infection, starting ART, and also as a consequence ofstigmatization.The average scores obtained for the WHOQOL-HIV bref domains were similar to those foundin other studies addressing people living with AIDS, highlighting an intermediateperception of QoL-14. Non-,,-14.(-).In the context of MSDH, homosexual men obtained low average scores in regard tospirituality (p=0.037), the domain that refers to forgiveness and blame, concerns overthe future, death and dying. This finding reflects the early days of HIV/AIDS, duringwhich the infection was attributed to risk groups, especially homosexual individuals, inaddition to the fact that infection meant death, a situation which was later changed dueto the advent of ART, which led to increased survival rates for people withAIDS-11.per capita income of those living in thesame household.Married men scored lower than single men, on average, in regard to domain V (p=0.077),which refers to physical safety, housing, finance, access to health and social care, theability to acquire information and learn new skills, leisure, environment and transport.This result may be explained by the fact that married men have to provide for theirfamilies, which decreases the ousehold.(-).Those who did not profess a religion scored higher than Catholics in domains I(p=0.005), II (p=0.017) and III (p=0.038). This finding contrasts with relatedliterature, which shows positive correlation between health and spirituality as having areligion supports and strengthens the individual in the face of the adversities imposedby pathological conditions. Additionally, AIDS represents, in the social sphere, aseries of disparaging metaphors such as associations with punishment, which would amountto being convicted for socially disapproved behaviors-19..Living with a partner also increased the perception of QoL in regard to domain V(p=0.049). This aspect may be related to social support, which indicates the influenceof social interactions with the well-being and health of people. Due to stigma, however,a seropositive status for HIV may hinder social support specifically related to thedisease.per capita income greater than three times theminimum wage increased the average values of scores in regard to domain V when comparedto people's per capita income of below one times the minimum wage(p=0.003) and between one and two times the minimum wage (p=0.042).Having a formal job increased the average scores obtained for domains II (p=0.045) andIII (p=0.023), while .Given the previous discussion, the social inclusion of people with HIV in the workenvironment has a considerable positive impact on QoL. What is observed, however, isdiscrimination both on the part of employers and co-workers. This fact culminates indenying to these people the most elementary right, the right to work. Since the 1990s inBrazil, an inter-ministerial decree prohibits, in the sphere of federal public service,the requirement of HIV tests in pre-hiring exams and in periodic health exams, becausebeing HIV-positive does not cause loss of working capacity and social and/orprofessional contact with these individuals does not constitute a risk ofinfection.. This layer was not included in the data collection, which may be seen as alimitation of this study. The lack of inclusion was because the study's participants donot recognize the more general macro-determinants or aspects of the society to whichthey belong, including understanding of health policies directed to the prevention,control, and treatment of HIV/AIDS infection.As for layer 5, we have the distal or macro-determinants, represented by society'seconomic, cultural, and environmental conditions. This l.In this context, initially, due to a lack of a public policy structured by the Stateaiming to fight HIV/AIDS, a large number of Non-Governmental Organizations (ONGs)emerged in the country to fight the disease. This coping policy gained momentum byreaching various social groups, when civil society mobilized and ensured its priority,political pressure to accomplish it and funding for it. Currently, Brazil has one of themost progressive policies to cope with HIV/AIDS and is a point of reference for theworld..The current policy concerning the prevention, treatment and control of HIV/AIDS is aresult of the epidemic's social and historical construction. The first discussionsconcerning its control were directed to the identification of risk factors, a conceptthat is no longer used because it resulted in the stigmatization of certain groups, suchas homosexuals. Later, it was replaced by the concept of risk behavior, which blamed thepopulation for failures in preventing HIV/AIDS. Hence, these approaches were inefficientand did not favor coping with the epidemic, for they did not consider social, culturaland contextual determinants.. This means that, in addition to groups initially affected by HIV/AIDS,such as homosexuals, sex workers, intravenous drug users and hemophiliacs, people instable relationships with a risk behavior and who do not use condoms, adolescents,elderly individuals, those with a low level of education, low income, and living in theinterior of the country are also taken into account.The epidemic in Brazil is currently stable and the concept of vulnerability began to beconsidered in the context of HIV/AIDS, since the epidemic is centered in vulnerablepopulation subgroups,18. Tount,,-23.The use of MSDH and the application of the WHOQOL-HIV bref enabled identifying theperceptions of QoL held by men with AIDS, who for the most part considered their QoL tobe intermediate. This finding shows that despite the existence of policies concerningaccess to ART and to healthcare provided in the public health network, other aspectssuch as social determinants of health should be considered for the populations intowhich HIV has been disseminated.Studies of this nature are important to understanding the context in which individualswith HIV/AIDS are inserted because the lives of these individuals can be seen from amultidimensional perspective and interventions can thereby be more efficient.Statistical associations concerning category of exposure, marital status, religion, jobcontract, and income were observed, confirming the importance of social determinants ofhealth in impacting the way men experience the process of health and disease.We stress the importance of this study for understanding the context of those livingwith AIDS, since it can contribute to the delivery of care. Note that further studiesare needed to contribute to the QoL of these individuals and reduce morbidity andmortality. Hence, even through there is no cure, HIV infection and AIDS can effectivelybe considered chronic conditions.